AbstractThe non-polymorphic HLA-E molecule offers opportunities for new universal immunotherapeutic approaches to chronic infectious diseases. Chronic Hepatitis B virus (HBV) infection is driven in part by T cell dysfunction due to elevated levels of the HBV envelope (Env) protein hepatitis B surface antigen (HBsAg).

摘要非多态性HLA-E分子为慢性传染病的新的通用免疫治疗方法提供了机会。慢性乙型肝炎病毒（HBV）感染的部分原因是由于HBV包膜（Env）蛋白乙型肝炎表面抗原（HBsAg）水平升高导致的T细胞功能障碍。

Here we report the characterization of three genotypic variants of an HLA-E-binding HBsAg peptide, Env371-379, identified through bioinformatic predictions and verified by biochemical and cellular assays. Using a soluble affinity-enhanced T cell receptor (TCR) (a09b08)-anti-CD3 bispecific molecule to probe HLA-E presentation of the Env371-379 peptides, we demonstrate that only the most stable Env371-379 variant, L6I, elicits functional responses to a09b08-anti-CD3-redirected polyclonal T cells co-cultured with targets expressing endogenous HBsAg.

在这里，我们报告了通过生物信息学预测鉴定并通过生化和细胞测定验证的HLA-E结合HBsAg肽Env371-379的三种基因型变体的表征。使用可溶性亲和力增强的T细胞受体（TCR）（a09b08）-抗CD3双特异性分子来探测Env371-379肽的HLA-E呈递，我们证明只有最稳定的Env371-379变体L6I引发对与表达内源性HBsAg的靶标共培养的a09b08-抗CD3-重定向的多克隆T细胞的功能反应。

Furthermore, HLA-E-Env371-379 L6I-specific CD8+ T cells are detectable in HBV-naïve donors and people with chronic HBV after in vitro priming. In conclusion, we provide evidence for HLA-E-mediated HBV Env peptide presentation, and highlight the effect of viral mutations on the stability and targetability of pHLA-E molecules..

此外，HLA-E-Env371-379 L6I特异性CD8+T细胞在体外引发后在HBV初治供体和慢性HBV患者中可检测到。总之，我们为HLA-E介导的HBV Env肽呈递提供了证据，并强调了病毒突变对pHLA-E分子稳定性和靶向性的影响。。

IntroductionApproximately 2 billion people worldwide are infected with the hepatotropic Hepatitis B virus (HBV), with nearly 300 million being chronically infected. The annual mortality associated with chronic HBV infection is around 820,000 people, primarily from cirrhosis and hepatocellular carcinoma (HCC)1,2.

引言全世界约有20亿人感染了嗜肝乙型肝炎病毒（HBV），其中近3亿人长期感染。与慢性HBV感染相关的年死亡率约为820000人，主要来自肝硬化和肝细胞癌（HCC）1,2。

HCC is the sixth most common cancer and the fourth leading cause of cancer-related death globally, with almost 50% of cases associated with chronic HBV infection3,4,5. Although a highly effective vaccine is widely available and has led to a decline in acute and chronic HBV infections (CHB) worldwide, ~1.5 million new infections occur annually, and up to 15% of vaccinated individuals do not acquire protection against HBV infection2,6.CHB is defined by the detection of circulating envelope protein hepatitis B surface antigen (HBsAg) or HBV DNA for more than 6 months.

HCC是全球第六大常见癌症，也是全球第四大癌症相关死亡原因，近50%的病例与慢性HBV感染有关3,4,5。虽然一种高效疫苗已被广泛使用，并导致全世界急性和慢性HBV感染（CHB）的下降，但每年约有150万例新感染发生，高达15%的接种疫苗的个体无法获得针对HBV感染的保护2,6.CHB的定义是检测循环包膜蛋白乙型肝炎表面抗原（HBsAg）或HBV DNA超过6个月。

The major impediments to achieving a cure for HBV are the persistence of covalently closed circular DNA (cccDNA) located in the hepatocyte nucleus, which serves as a transcriptional template for various HBV RNAs, and the integration of HBV DNA into the host genome, which is a source of secreted HBsAg.

实现HBV治愈的主要障碍是位于肝细胞核中的共价闭合环状DNA（cccDNA）的持久性，其作为各种HBV RNA的转录模板，以及HBV DNA整合到宿主基因组中，这是分泌的HBsAg的来源。

Currently approved therapies for CHB are (1) nucleos(t)ide analogs (NAs), which suppress HBV replication but do not eliminate the viral reservoir and thus are a lifelong treatment; (2) pegylated interferon alpha-2a, which can drive cccDNA degradation leading to a cure in ~10% patients following a finite course of therapy but with limited use due to severe adverse effects.

目前批准的CHB治疗方法是（1）核苷类似物（NAs），其抑制HBV复制但不消除病毒库，因此是终身治疗；（2） 聚乙二醇化干扰素α-2a，可以驱动cccDNA降解，从而在有限的治疗过程中治愈约10%的患者，但由于严重的不良反应而使用有限。

These treatments reduce the risk of cirrhosis, liver failure, and HCC, but rarely lead to sustained loss of HBsAg and undetectable HBV DNA in serum after completion of treatment, which are prerequisites for a functional cure7,8,9. Thus,.

。因此，。

Data availability

数据可用性

The crystallography data generated in this study have been deposited in the RCSB protein data bank (PDB) with the accession codes 8RLT, 8RLU, and 8RLV. All data are included in the Supplementary Information or available from the authors, as are unique reagents used in this Article. The raw numbers for charts and graphs are available in the Source Data file whenever possible. Source data are provided with this paper..

本研究中产生的晶体学数据已保存在RCSB蛋白质数据库（PDB）中，登录号为8RLT，8RLU和8RLV。所有数据均包含在补充信息中或可从作者处获得，以及本文中使用的独特试剂。只要有可能，图表和图形的原始数字都可以在源数据文件中找到。本文提供了源数据。。

Code availability

代码可用性

Scripts for data processing and analysis are publicly available at https://github.com/Immunocore/FindPeptideOrthologs.

数据处理和分析的脚本可在https://github.com/Immunocore/FindPeptideOrthologs.

ReferencesWHO. Hepatitis B. https://www.who.int/news-room/fact-sheets/detail/hepatitis-b (2024).Jeng, W.-J., Papatheodoridis, G. V. & Lok, A. S. F. Hepatitis B. Lancet 401, 1039–1052 (2023).Article

参考WHO。乙型肝炎。https://www.who.int/news-room/fact-sheets/detail/hepatitis-b（2024年）。Jeng，W.-J.，Papatheodoridis，G.V.＆Lok，A.S.F。乙型肝炎。柳叶刀4011039-1052（2023）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

El-Serag, H. B. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology 142, 1264–1273.e1 (2012).Article

。胃肠病学1421264-1273.e1（2012）。文章

PubMed

PubMed

Google Scholar

谷歌学者

Xie, Y. Infectious agents associated cancers: epidemiology and molecular biology. Adv. Exp. Med. Biol. 1018, 11–21 (2017).Article

Xie，Y。与传染源相关的癌症：流行病学和分子生物学。高级实验医学生物学。1018,11-21（2017）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Bray, F. et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 68, 394–424 (2018).Article

Bray，F.等人，《2018年全球癌症统计：GLOBOCAN对185个国家36种癌症的全球发病率和死亡率的估计》。CA Cancer J.Clin。68394-424（2018）。文章

PubMed

PubMed

Google Scholar

谷歌学者

Roome, A. J., Walsh, S. J., Cartter, M. L. & Hadler, J. L. Hepatitis B vaccine responsiveness in connecticut public safety personnel. JAMA 270, 2931–2934 (1993).Article

Roome，A.J.，Walsh，S.J.，Cartter，M.L。和Hadler，J.L。康涅狄格州公共安全人员的乙型肝炎疫苗反应性。JAMA 2702931–2934（1993）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Yuen, M.-F. et al. Hepatitis B virus infection. Nat. Rev. Dis. Prim. 4, 18035 (2018).Article

Yuen，M.-F.等人。乙型肝炎病毒感染。自然版本Dis。一本正经。418035（2018）。文章

PubMed

PubMed

Google Scholar

谷歌学者

Mak, L.-Y., Cheung, K.-S., Fung, J., Seto, W.-K. & Yuen, M.-F. New strategies for the treatment of chronic hepatitis B. Trends Mol. Med. https://doi.org/10.1016/j.molmed.2022.06.002 (2022).Article

Mak，L.-Y.，Cheung，K.-S.，Fung，J.，Seto，W.-K.＆Yuen，M.-F.治疗慢性乙型肝炎的新策略。Trends Mol.Med。https://doi.org/10.1016/j.molmed.2022.06.002（2022年）。文章

PubMed

PubMed

Google Scholar

谷歌学者

Lau, G. K. K. et al. Peginterferon alfa-2a, lamivudine, and the combination for HBeAg-positive chronic hepatitis B. N. Engl. J. Med. 352, 2682–2695 (2005).Article

Lau，G.K.K.等人。聚乙二醇干扰素α-2a、拉米夫定及其联合治疗HBeAg阳性慢性乙型肝炎。N.Engl。J、 医学杂志3522682-2695（2005）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Feld, J. J., Lok, A. S. & Zoulim, F. New perspectives on development of curative strategies for chronic hepatitis B. Clin. Gastroenterol. Hepatol. 21, 2040–2050 (2023).Article

Feld，J.J.，Lok，A.S.＆Zoulim，F。慢性乙型肝炎治疗策略发展的新观点。临床。胃肠道。肝病。212040-2050（2023）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Burwitz, B. J. et al. MHC-E–restricted CD8+ T cells target hepatitis B virus–infected human hepatocytes. J. Immunol. 204, 2169–2176 (2020).Article

Burwitz，B.J。等人，MHC-E限制性CD8+T细胞靶向乙型肝炎病毒感染的人肝细胞。J、 免疫。2042169-2176（2020）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Chisari, F. V. & Ferrari, C. Hepatitis B virus immunopathogenesis. Annu. Rev. Immunol. 13, 29–60 (1995).Article

Chisari，F.V。和Ferrari，C。乙型肝炎病毒免疫发病机制。。修订版Immunol。13，29–60（1995）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Boni, C. et al. Characterization of hepatitis B virus (HBV)-specific T-cell dysfunction in chronic HBV infection. J. Virol. 81, 4215–4225 (2007).Article

Boni，C。等人。慢性HBV感染中乙型肝炎病毒（HBV）特异性T细胞功能障碍的表征。J、 维罗尔。814215-4225（2007）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Park, J.-J. et al. Hepatitis B virus–specific and global T-cell dysfunction in chronic hepatitis B. Gastroenterology 150, 684–695.e5 (2016).Article

Park，J.-J.等人，《慢性乙型肝炎中乙型肝炎病毒特异性和全球T细胞功能障碍》。胃肠病学150684-695.e5（2016）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Jeng, W.-J. & Lok, A. S. F. What will it take to cure hepatitis B? Hepatol. Commun. 7, e0084 (2023).Article

Jeng，W.-J.＆Lok，A.S.F。治疗乙型肝炎需要什么？肝病。Commun公司。7，e0084（2023）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Liddy, N. et al. Monoclonal TCR-redirected tumor cell killing. Nat. Med. 18, 980–987 (2012).Article

Liddy，N。等人。单克隆TCR重定向肿瘤细胞杀伤。《自然医学》18980-987（2012）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Fergusson, J. R. et al. Immune‐mobilizing monoclonal T cell receptors mediate specific and rapid elimination of hepatitis B–infected cells. Hepatology 72, 1528–1540 (2020).Article

Fergusson，J.R.等人。免疫动员单克隆T细胞受体介导特异性和快速消除乙型肝炎感染细胞。肝病学721528-1540（2020）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Boudousquie, C. et al. Polyfunctional response by ImmTAC (IMCgp100) redirected CD8+ and CD4+ T cells. Immunology 152, 425–438 (2017).Article

。免疫学152425-438（2017）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Nathan, P. et al. Overall survival benefit with tebentafusp in metastatic uveal melanoma. New Engl. J. Med. 385, 1196–1206 (2021).Article

Nathan，P。等人。替本福斯治疗转移性葡萄膜黑色素瘤的总体生存获益。新英语。J、 医学3851196-1206（2021）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Bourgeois, S. et al. Study of IMC-I109V in non-cirrhotic HBeAg-negative chronic HBV infection. NCT05867056 https://easl.eu/wp-content/uploads/2022/06/ILC-2022-Abstract-Book_Version-4_25June2022_red.pdf (2022).Ltd, I. Study of IMC-I109V in non-cirrhotic HBeAg-negative chronic HBV infection.

Bourgeois，S.等。IMC-I109V在非肝硬化HBeAg阴性慢性HBV感染中的研究。NCT05867056https://easl.eu/wp-content/uploads/2022/06/ILC-2022-Abstract-Book_Version-4_25June2022_red.pdf（2022年）。Ltd，I。IMC-I109V在非肝硬化HBeAg阴性慢性HBV感染中的研究。

NCT05867056 https://clinicaltrials.gov/study/NCT05867056.Geraghty, D. E., Stockschleader, M., Ishitani, A. & Hansen, J. A. Polymorphism at the HLA-E locus predates most HLA-A and -B polymorphism. Hum. Immunol. 33, 174–184 (1992).Article .

NCT05867056https://clinicaltrials.gov/study/NCT05867056.Geraghty，D.E.，Stockschleader，M.，Ishitani，A。＆Hansen，J.A。HLA-E基因座的多态性早于大多数HLA-A和B多态性。嗯，免疫。33174-184（1992）。文章。

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Grimsley, C. & Ober, C. Population genetic studies of HLA-E evidence for selection. Hum. Immunol. 52, 33–40 (1997).Article

Grimsley，C。＆Ober，C。HLA-E选择证据的群体遗传学研究。嗯，免疫。52，33-40（1997）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Olieslagers, T. I. et al. New insights in HLA‐E polymorphism by refined analysis of the full‐length gene. HLA 89, 143–149 (2017).Article

Olieslagers，T.I.等人。通过对全长基因的精细分析，对HLA-E多态性的新见解。HLA 89143-149（2017）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Braud, V., Jones, E. Y. & McMichael, A. The human major histocompatibility complex class Ib molecule HLA‐E binds signal sequence‐derived peptides with primary anchor residues at positions 2 and 9. Eur. J. Immunol. 27, 1164–1169 (1997).Article

Braud，V.，Jones，E.Y。＆McMichael，A。人类主要组织相容性复合物Ib类分子HLA-E将信号序列衍生的肽与位置2和9处的主要锚定残基结合。欧洲免疫学杂志。271164-1169（1997）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Lin, Z. et al. HLA class I signal peptide polymorphism determines the level of CD94/NKG2–HLA-E-mediated regulation of effector cell responses. Nat. Immunol. https://doi.org/10.1038/s41590-023-01523-z (2023).Borrego, F., Ulbrecht, M., Weiss, E. H., Coligan, J. E. & Brooks, A. G. Recognition of human histocompatibility leukocyte antigen (HLA)-E complexed with HLA class I signal sequence–derived peptides by CD94/NKG2 confers protection from natural killer cell–mediated lysis.

Lin，Z。等人。HLA I类信号肽多态性决定了CD94/NKG2-HLA-E介导的效应细胞反应调节水平。自然免疫。https://doi.org/10.1038/s41590-023-01523-z（2023年）。Borrego，F.，Ulbrecht，M.，Weiss，E.H.，Coligan，J.E。＆Brooks，A.G。通过CD94/NKG2识别与HLA I类信号序列衍生肽复合的人类组织相容性白细胞抗原（HLA）-E赋予免受自然杀伤细胞介导的裂解的保护。

J. Exp. Med. 187, 813–818 (1998).Article .

J、 实验医学187813-818（1998）。文章。

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Braud, V. M. et al. HLA-E binds to natural killer cell receptors CD94/NKG2A, B and C. Nature 391, 795–799 (1998).Article

Braud，V.M.等人，《HLA-E与自然杀伤细胞受体CD94/NKG2A，B和C结合》。Nature 391795-799（1998）。文章

ADS

广告

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Heinzel, A. S. et al. HLA-E–dependent presentation of Mtb-derived antigen to human CD8+ T cells. J. Exp. Med. 196, 1473–1481 (2002).Article

Heinzel，A.S.等人。Mtb衍生抗原向人CD8+T细胞的HLA-E依赖性呈递。J、 实验医学1961473-1481（2002）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Pietra, G. et al. HLA-E-restricted recognition of cytomegalovirus-derived peptides by human CD8+ cytolytic T lymphocytes. Proc. Natl Acad. Sci. USA 100, 10896–10901 (2003).Article

Pietra，G。等人。HLA-E限制了人CD8+溶细胞T淋巴细胞对巨细胞病毒衍生肽的识别。程序。国家科学院。科学。美国10010896–10901（2003）。文章

ADS

广告

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Joosten, S. A. et al. Mycobacterium tuberculosis peptides presented by HLA-E molecules are targets for human CD8+ T-cells with cytotoxic as well as regulatory activity. PLos Pathog. 6, e1000782 (2010).Article

由HLA-E分子呈递的结核分枝杆菌肽是具有细胞毒性和调节活性的人CD8+T细胞的靶标。PLos Pathog。6，e1000782（2010）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Hammer, Q. et al. SARS-CoV-2 Nsp13 encodes for an HLA-E-stabilizing peptide that abrogates inhibition of NKG2A-expressing NK cells. Cell Rep. 38, 110503 (2022).Article

Hammer，Q。等人。SARS-CoV-2 Nsp13编码一种HLA-E稳定肽，可消除对表达NKG2A的NK细胞的抑制作用。Cell Rep.38110503（2022）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Salerno-Gonçalves, R., Fernandez-Viña, M., Lewinsohn, D. M. & Sztein, M. B. Identification of a human HLA-E-restricted CD8+ T cell subset in volunteers immunized with Salmonella enterica Serovar Typhi strain Ty21a typhoid vaccine. J. Immunol. 173, 5852–5862 (2004).Article

Salerno Gonçalves，R.，Fernandez-Viña，M.，Lewinsohn，D.M。＆Sztein，M.B。在用肠炎沙门氏菌血清型伤寒菌株Ty21a伤寒疫苗免疫的志愿者中鉴定人HLA-E限制性CD8+T细胞亚群。J、 免疫。1735852-5862（2004）。文章

PubMed

PubMed

Google Scholar

谷歌学者

Yang, H. et al. HLA-E–restricted SARS-CoV-2–specific T cells from convalescent COVID-19 patients suppress virus replication despite HLA class Ia down-regulation. Sci. Immunol. 8, eabl8881 (2023).Article

Yang，H。等人。尽管HLA Ia类下调，但来自恢复期COVID-19患者的HLA-E限制性SARS-CoV-2特异性T细胞抑制病毒复制。科学。免疫。8，eabl8881（2023）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Yang, H. et al. HLA-E–restricted, Gag-specific CD8+ T cells can suppress HIV-1 infection, offering vaccine opportunities. Sci. Immunol. 6, eabg1703 (2021).Article

Yang，H。等人。HLA-E限制的，Gag特异性的CD8+T细胞可以抑制HIV-1感染，提供疫苗接种机会。科学。免疫。。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Barber, C. et al. Structure‐guided stabilization of pathogen‐derived peptide‐HLA‐E complexes using non‐natural amino acids conserves native TCR recognition. Eur. J. Immunol. https://doi.org/10.1002/eji.202149745 (2022).Article

Barber，C。等人。使用非天然氨基酸对病原体衍生的肽-HLA-E复合物进行结构引导的稳定化可保存天然TCR识别。欧洲免疫学杂志。https://doi.org/10.1002/eji.202149745（2022年）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Moysey, R. K. et al. High affinity soluble ILT2 receptor: a potent inhibitor of CD8+ T cell activation. Protein Cell 1, 1118–1127 (2010).Article

Moysey，R.K.等人。高亲和力可溶性ILT2受体：CD8+T细胞活化的有效抑制剂。。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Liu, Q. et al. In vivo therapeutic effects of affinity-improved-TCR engineered T-cells on HBV-related hepatocellular carcinoma. J. Immunother. Cancer 8, e001748 (2020).Article

。J、 免疫疗法。癌症8，e001748（2020）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Walters, L. C. et al. Pathogen-derived HLA-E bound epitopes reveal broad primary anchor pocket tolerability and conformationally malleable peptide binding. Nat. Commun. 9, 3137 (2018).Article

Walters，L.C。等人。病原体衍生的HLA-E结合表位揭示了广泛的主要锚口袋耐受性和构象可塑性肽结合。国家公社。93137（2018）。文章

ADS

广告

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

O’Callaghan, C. A. et al. Structural features impose tight peptide binding specificity in the nonclassical MHC molecule HLA-E. Mol. Cell 1, 531–541 (1998).Article

O'Callaghan，C.A。等人。结构特征在非经典MHC分子HLA-E中施加了紧密的肽结合特异性。分子细胞1531-541（1998）。文章

PubMed

PubMed

Google Scholar

谷歌学者

Chen, C.-C. et al. Pacbio sequencing of PLC/PRF/5 cell line and clearance of HBV integration through CRISPR/Cas-9 system. Front. Mol. Biosci. 8, 676957 (2021).Article

Chen，C.-C.等。PLC/PRF/5细胞系的Pacbio测序和通过CRISPR/Cas-9系统清除HBV整合。正面。。8676957（2021年）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Edman, J. C., Gray, P., Valenzuela, P., Rall, L. B. & Rutter, W. J. Integration of hepatitis B virus sequences and their expression in a human hepatoma cell. Nature 286, 535–538 (1980).Article

Edman，J.C.，Gray，P.，Valenzuela，P.，Rall，L.B。＆Rutter，W.J。乙型肝炎病毒序列的整合及其在人肝癌细胞中的表达。自然286535-538（1980）。文章

ADS

广告

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

MacNab, G. M., Alexander, J. J., Lecatsas, G., Bey, E. M. & Urbanowicz, J. M. Hepatitis B surface antigen produced by a human hepatoma cell line. Br. J. Cancer 34, 509–515 (1976).Article

MacNab，G.M.，Alexander，J.J.，Lecatsas，G.，Bey，E.M。＆Urbanowicz，J.M。由人肝癌细胞系产生的乙型肝炎表面抗原。Br.J.Cancer 34509-515（1976）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Bowcock, A. M. et al. The PLC/PRF/5 human hepatoma cell line. II. Chromosomal assignment of hepatitis B virus integration sites. Cancer Genet. Cytogenet. 18, 19–26 (1985).Article

Bowcock，A.M.等人，PLC/PRF/5人肝癌细胞系。二。乙型肝炎病毒整合位点的染色体分配。癌症基因。细胞遗传学。18，19-26（1985）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Sozzi, V. et al. In vitro studies show that sequence variability contributes to marked variation in hepatitis B virus replication, protein expression, and function observed across genotypes. J. Virol. 90, 10054–10064 (2016).Article

Sozzi，V。等人的体外研究表明，序列变异性有助于在不同基因型中观察到的乙型肝炎病毒复制，蛋白质表达和功能的显着变化。J、 维罗尔。9010054-10064（2016）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Paterson, R. L. et al. An HLA-E-targeted TCR bispecific molecule redirects T cell immunity against Mycobacterium tuberculosis. Proc. Natl Acad. Sci. USA 121, e2318003121 (2024).Article

Paterson，R.L。等人。一种靶向HLA-E的TCR双特异性分子重定向针对结核分枝杆菌的T细胞免疫。程序。国家科学院。科学。美国121，E231800321（2024）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Strong, R. K. et al. HLA-E allelic variants. Correlating differential expression, peptide affinities, crystal structures, and thermal stabilities. J. Biol. Chem. 278, 5082–5090 (2003).Article

Strong，R.K.等人，HLA-E等位基因变体。关联差异表达，肽亲和力，晶体结构和热稳定性。J、 生物。化学。。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Nattermann, J. et al. The HLA-A2 restricted T cell epitope HCV core35–44 stabilizes HLA-E expression and inhibits cytolysis mediated by natural killer cells. Am. J. Pathol. 166, 443–453 (2005).Article

Nattermann，J。等人。HLA-A2限制性T细胞表位HCV核心35-44稳定HLA-E表达并抑制自然杀伤细胞介导的细胞溶解。美国J.Pathol。166443-453（2005）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Lampen, M. H. et al. Alternative peptide repertoire of HLA-E reveals a binding motif that is strikingly similar to HLA-A2. Mol. Immunol. 53, 126–131 (2013).Article

Lampen，M.H。等人。HLA-E的替代肽库揭示了与HLA-A2惊人相似的结合基序。分子免疫。53126-131（2013）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Bouezzedine, F., Fardel, O. & Gripon, P. Interleukin 6 inhibits HBV entry through NTCP down regulation. Virology 481, 34–42 (2015).Article

Bouezzedine，F.，Fardel，O。＆Gripon，P。白细胞介素6通过NTCP下调抑制HBV进入。病毒学481,34-42（2015）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Hösel, M. et al. Not interferon, but interleukin‐6 controls early gene expression in hepatitis B virus infection. Hepatology 50, 1773–1782 (2009).Article

Hösel，M。等人。不是干扰素，而是白细胞介素-6控制乙型肝炎病毒感染的早期基因表达。肝病学501773-1782（2009）。文章

PubMed

PubMed

Google Scholar

谷歌学者

Sun, C. et al. High NKG2A expression contributes to NK cell exhaustion and predicts a poor prognosis of patients with liver cancer. Oncoimmunology 6, e1264562 (2017).Article

Sun，C。等人。NKG2A的高表达会导致NK细胞衰竭，并预测肝癌患者的预后不良。肿瘤免疫学6，e1264562（2017）。文章

PubMed

PubMed

Google Scholar

谷歌学者

Hamid, M. A. et al. Enriched HLA-E and CD94/NKG2A interaction limits antitumor CD8+ tumor-infiltrating T lymphocyte responses. Cancer Immunol. Res. 7, 1293–1306 (2019).Article

。癌症免疫。第71293-1306号决议（2019年）。文章

ADS

广告

CAS

中科院

Google Scholar

谷歌学者

Bansal, A. et al. HLA-E–restricted HIV-1–specific CD8+ T cell responses in natural infection. J. Clin. Invest. 131, e148979 (2021).Hogan, M. J. et al. Cryptic MHC-E epitope from influenza elicits a potent cytolytic T cell response. Nat. Immunol. https://doi.org/10.1038/s41590-023-01644-5 (2023).Wallace, Z.

Bansal，A。等人。自然感染中HLA-E限制性HIV-1特异性CD8+T细胞反应。J、 临床。投资。131，e148979（2021）。来自流感的隐性MHC-E表位引发有效的细胞溶解性T细胞应答。自然免疫。https://doi.org/10.1038/s41590-023-01644-5（2023年）。华莱士，Z。

et al. Instability of the HLA-E peptidome of HIV presents a major barrier to therapeutic targeting. Mol. Ther. https://doi.org/10.1016/j.ymthe.2024.01.010 (2024).Article .

HIV的HLA-E肽组的不稳定性是治疗靶向的主要障碍。摩尔热。https://doi.org/10.1016/j.ymthe.2024.01.010（2024年）。文章。

PubMed

PubMed

Google Scholar

谷歌学者

Jurtz, V. et al. NetMHCpan-4.0: improved peptide–MHC class I interaction predictions integrating eluted ligand and peptide binding affinity data. J. Immunol. 199, 3360–3368 (2017).Article

Jurtz，V。等人。NetMHCpan-4.0：整合洗脱配体和肽结合亲和力数据的改进的肽-MHC I类相互作用预测。J、 免疫。1993360-3368（2017）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Velkov, S., Ott, J. J., Protzer, U. & Michler, T. The global hepatitis B virus genotype distribution approximated from available genotyping data. Genes 9, 495 (2018).Article

Velkov，S.，Ott，J.J.，Protzer，U。和Michler，T。全球乙型肝炎病毒基因型分布近似于可用的基因分型数据。基因9495（2018）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Walker, A. & Treveil, A. Viral sequence determines HLA-E-restricted T cell recognition of hepatitis B surface antigen. FindPeptideOrthologs https://doi.org/10.5281/zenodo.13912475 (2024).Article

Walker，A。＆Treveil，A。病毒序列决定了HLA-E限制性T细胞对乙型肝炎表面抗原的识别。FindPeptideOrthologs公司https://doi.org/10.5281/zenodo.13912475（2024年）。文章

Google Scholar

谷歌学者

Winter, G. et al. DIALS: implementation and evaluation of a new integration package. Acta Crystallogr. D Struct. Biol. 74, 85–97 (2018).Article

Winter，G.等人，《拨号：新集成包的实施和评估》。晶体学报。D结构。生物学杂志74,85-97（2018）。文章

ADS

广告

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Winter, G. xia2: an expert system for macromolecular crystallography data reduction. J. Appl. Crystallogr. 43, 186–190 (2010).Article

Winter，G.xia2：用于大分子晶体学数据简化的专家系统。J、 应用。。43186-190（2010）。文章

ADS

广告

CAS

中科院

Google Scholar

谷歌学者

Liebschner, D. et al. Macromolecular structure determination using X‐rays, neutrons and electrons: recent developments in Phenix. Acta Crystallogr. D Struct. Biol. 75, 861–877 (2019).Article

Liebschner，D.等人，《利用X射线、中子和电子测定大分子结构：Phenix的最新进展》。晶体学报。D结构。生物学75861-877（2019）。文章

ADS

广告

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Emsley, P., Lohkamp, B., Scott, W. G. & Cowtan, K. Features and development of Coot. Acta Crystallogr. D Struct. Biol. 66, 486–501 (2010).Article

Emsley，P.，Lohkamp，B.，Scott，W.G。和Cowtan，K。Coot的特征和发展。晶体学报。D结构。生物学66486-501（2010）。文章

ADS

广告

CAS

中科院

Google Scholar

谷歌学者

Murshudov, G. N. et al. REFMAC5 for the refinement of macromolecular crystal structures. Acta Crystallogr. D Biol. Crystallogr. 67, 355–367 (2011).Article

Murshudov，G.N。等人，REFMAC5，用于改进大分子晶体结构。晶体学报。D生物晶体学。67355-367（2011）。文章

ADS

广告

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Winn, M. D. et al. Overview of the CCP4 suite and current developments. Acta Crystallogr. D Biol. Crystallogr. 67, 235–242 (2011).Article

Winn，M.D.等人，《CCP4套件概述和当前发展》。晶体学报。D生物晶体学。67235-242（2011）。文章

ADS

广告

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Joosten, R. P., Joosten, K., Murshudov, G. N. & Perrakis, A. PDB_REDO: constructive validation, more than just looking for errors. Acta Crystallogr. D Biol. Crystallogr. 68, 484–496 (2012).Article

Joosten，R.P.，Joosten，K.，Murshudov，G.N。＆Perrakis，A。PDB\U重做：建设性验证，不仅仅是寻找错误。晶体学报。D生物晶体学。68484-496（2012）。文章

ADS

广告

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

MacLean, B. et al. Skyline: an open source document editor for creating and analyzing targeted proteomics experiments. Bioinformatics 26, 966–968 (2010).Article

Skyline：用于创建和分析目标蛋白质组学实验的开源文档编辑器。生物信息学26966-968（2010）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Chiang, T.-W. W., Sage, Cle, Larrieu, D., Demir, M. & Jackson, S. P. CRISPR-Cas9D10A nickase-based genotypic and phenotypic screening to enhance genome editing. Sci. Rep. 6, 24356 (2016).Article

Chiang，T.-W.W.，Sage，Cle，Larrieu，D.，Demir，M。＆Jackson，S.P。基于CRISPR-Cas9D10A切口酶的基因型和表型筛选，以增强基因组编辑。科学。代表624356（2016）。文章

ADS

广告

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Chook, J. B. et al. Universal primers for detection and sequencing of hepatitis B virus genomes across genotypes A to G. J. Clin. Microbiol. 53, 1831–1835 (2015).Article

Chook，J.B.等人。用于检测和测序跨越基因型A至G.J.Clin的乙型肝炎病毒基因组的通用引物。微生物。531831-1835（2015）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Gencay, M. et al. Ultra-deep sequencing reveals high prevalence and broad structural diversity of hepatitis B surface antigen mutations in a global population. PLoS ONE 12, e0172101 (2017).Article

Gencay，M。等人。超深度测序揭示了全球人群中乙型肝炎表面抗原突变的高患病率和广泛的结构多样性。PLoS ONE 12，e0172101（2017）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Download referencesAcknowledgementsThe authors would like to thank Andrew Sewell (Cardiff University) and Peter Revill (Melbourne Health) for providing reagents; Daniel Fonseca for figure generation; Kate Vowell for sourcing patient sample material; Hussein Al-Mossawi and JoAnn Suzich for critical review of the manuscript; Giovanna Bossi, Lorraine Whaley, Nicola Smith, and Marco Lepore for scientific input.Author informationAuthor notesThese authors contributed equally: Gavuthami Murugesan, Rachel L.

下载参考文献致谢作者要感谢Andrew Sewell（加的夫大学）和Peter Revill（墨尔本健康）提供试剂；Daniel Fonseca用于图形生成；Kate Vonell负责采购患者样本材料；侯赛因·莫萨维和乔安·苏齐奇对手稿进行了批判性审查；乔瓦娜·博西（GiovannaBossi）、洛林·惠利（LorraineWhaley）、尼古拉·史密斯（NicolaSmith）和马尔科·莱波尔（MarcoLepore）提供科学意见。作者信息作者注意到这些作者做出了同样的贡献：Gavuthami Murugesan，Rachel L。

Paterson.Authors and AffiliationsImmunocore Ltd, 92 Park Drive, Abingdon, Oxfordshire, OX14 4RY, UKGavuthami Murugesan, Rachel L. Paterson, Rakesh Kulkarni, Veronica Ilkow, Richard J. Suckling, Mary M. Connolly, Vijaykumar Karuppiah, Robert Pengelly, Archana Jadhav, Jose Donoso, Tiaan Heunis, Wilawan Bunjobpol, Gwilym Philips, Kafayat Ololade, Daniel Kay, Anshuk Sarkar, Claire Barber, Ritu Raj, Carole Perot, Tressan Grant, Agatha Treveil, Andrew Walker, Marcin Dembek, Dawn Gibbs-Howe, Miriam Hock, Ricardo J.

帕特森。作者和附属机构Simmunocore Ltd，92 Park Drive，Abingdon，Oxfordshire，OX14 4RY，UKGavuthami Murugesan，Rachel L.Paterson，Rakesh Kulkarni，Veronica Ilkow，Richard J.Suckling，Mary M.Connolly，Vijaykumar Karuppiah，Robert Pengelly，Archana Jadhav，Jose Donoso，Tiaan Heunis，Wilawan Bunjobbol，Gwilym Philips，Kafayat Ololade，Daniel Kay，Anshuk Sarkar，Claire Barber，Ritu Raj，Carole Perot，特雷桑·格兰特，阿加莎·特雷维，安德鲁·沃克，马辛·登贝克，道恩·吉布斯·豪，米里亚姆·霍克，里卡多·J。

Carreira, Kate E. Atkin, Lucy Dorrell, Andrew Knox, Sarah Leonard, Mariolina Salio & Luis F. GodinhoAuthorsGavuthami MurugesanView author publicationsYou can also search for this author in.

Carreira，Kate E.Atkin，Lucy Dorrell，Andrew Knox，Sarah Leonard，Mariolina Salio和Luis F.GodinhoAuthorsGavuthami MurugesanView作者出版物您也可以在中搜索这位作者。

PubMed Google ScholarRachel L. PatersonView author publicationsYou can also search for this author in

PubMed Google Scholarachel L.PatersonView作者出版物您也可以在

PubMed Google ScholarRakesh KulkarniView author publicationsYou can also search for this author in

PubMed Google Scholarakesh KulkarniView作者出版物您也可以在

PubMed Google ScholarVeronica IlkowView author publicationsYou can also search for this author in

PubMed Google ScholarVeronica IlkowView作者出版物您也可以在

PubMed Google ScholarRichard J. SucklingView author publicationsYou can also search for this author in

PubMed Google ScholarRichard J.SucklingView作者出版物您也可以在

PubMed Google ScholarMary M. ConnollyView author publicationsYou can also search for this author in

PubMed Google ScholarMary M.ConnollyView作者出版物您也可以在

PubMed Google ScholarVijaykumar KaruppiahView author publicationsYou can also search for this author in

PubMed Google ScholarVijaykumar KaruppiahView作者出版物您也可以在

PubMed Google ScholarRobert PengellyView author publicationsYou can also search for this author in

PubMed Google ScholarRobert PengellyView作者出版物您也可以在

PubMed Google ScholarArchana JadhavView author publicationsYou can also search for this author in

PubMed Google ScholararchanaJadhavview作者出版物您也可以在

PubMed Google ScholarJose DonosoView author publicationsYou can also search for this author in

PubMed谷歌学者Jose DonosoView作者出版物您也可以在

PubMed Google ScholarTiaan HeunisView author publicationsYou can also search for this author in

PubMed Google ScholarTiaan HeunisView作者出版物您也可以在

PubMed Google ScholarWilawan BunjobpolView author publicationsYou can also search for this author in

PubMed Google ScholarWilawan BunjobpolView作者出版物您也可以在

PubMed Google ScholarGwilym PhilipsView author publicationsYou can also search for this author in

PubMed Google ScholarGwilym PhilipsView作者出版物您也可以在

PubMed Google ScholarKafayat OloladeView author publicationsYou can also search for this author in

PubMed Google ScholarKafayat OloladeView作者出版物您也可以在

PubMed Google ScholarDaniel KayView author publicationsYou can also search for this author in

PubMed Google ScholardanielKayview作者出版物您也可以在

PubMed Google ScholarAnshuk SarkarView author publicationsYou can also search for this author in

PubMed Google ScholarAnshuk SarkarView作者出版物您也可以在

PubMed Google ScholarClaire BarberView author publicationsYou can also search for this author in

PubMed Google ScholarClaire BarberView作者出版物您也可以在

PubMed Google ScholarRitu RajView author publicationsYou can also search for this author in

PubMed Google ScholarRitu RajView作者出版物您也可以在

PubMed Google ScholarCarole PerotView author publicationsYou can also search for this author in

PubMed Google ScholarCarole PerotView作者出版物您也可以在

PubMed Google ScholarTressan GrantView author publicationsYou can also search for this author in

PubMed Google ScholarTressan GrantView作者出版物您也可以在

PubMed Google ScholarAgatha TreveilView author publicationsYou can also search for this author in

PubMed Google ScholarAgatha TreveilView作者出版物您也可以在

PubMed Google ScholarAndrew WalkerView author publicationsYou can also search for this author in

PubMed Google ScholarAndrew WalkerView作者出版物您也可以在

PubMed Google ScholarMarcin DembekView author publicationsYou can also search for this author in

PubMed Google ScholarMarcin DembekView作者出版物您也可以在

PubMed Google ScholarDawn Gibbs-HoweView author publicationsYou can also search for this author in

PubMed Google ScholarDawn Gibbs HoweView作者出版物您也可以在

PubMed Google ScholarMiriam HockView author publicationsYou can also search for this author in

PubMed谷歌学术评论HockView作者出版物您也可以在

PubMed Google ScholarRicardo J. CarreiraView author publicationsYou can also search for this author in

PubMed Google ScholarRicardo J.CarreiraView作者出版物您也可以在

PubMed Google ScholarKate E. AtkinView author publicationsYou can also search for this author in

PubMed Google ScholarKate E.AtkinView作者出版物您也可以在

PubMed Google ScholarLucy DorrellView author publicationsYou can also search for this author in

PubMed Google ScholarLucy DorrellView作者出版物您也可以在

PubMed Google ScholarAndrew KnoxView author publicationsYou can also search for this author in

PubMed Google ScholarAndrew Knoxiew作者出版物您也可以在

PubMed Google ScholarSarah LeonardView author publicationsYou can also search for this author in

PubMed Google ScholarSarah LeonardView作者出版物您也可以在

PubMed Google ScholarMariolina SalioView author publicationsYou can also search for this author in

PubMed Google ScholarMariolina SalioView作者出版物您也可以在

PubMed Google ScholarLuis F. GodinhoView author publicationsYou can also search for this author in

PubMed Google ScholarLuis F.GodinhoView作者出版物您也可以在

PubMed Google ScholarContributionsG.M., R.L.P., R.K., V.I., R.J.S., M.M.C., V.K., R.P., A.J., J.D., T.H., W.B., G.P., K.O., D.K., A.S., C.B., R.R., C.P., T.G., M.D., D.G., M.H., and L.F.G. performed the experimental studies. G.M., R.L.P., R.K., R.J.S., M.M.C., V.K., R.P., A.J., J.D., T.H., W.B., K.O., R.R., M.D., M.H., R.J.C., K.E.A., L.D., A.K., S.L., M.S., and L.F.G.

PubMed谷歌学术贡献。M、 ，R.L.P.，R.K.，V.I.，R.J.S.，M.M.C.，V.K.，R.P.，A.J.，J.D.，T.H.，W.B.，G.P.，K.O.，D.K.，A.S.，C.B.，R.R.，C.P.，T.G.，M.D.，D.G.，M.H.和L.F.G.进行了实验研究。G、 M.，R.L.P.，R.K.，R.J.S.，M.M.C.，V.K.，R.P.，A.J.，J.D.，T.H.，W.B.，K.O.，R.R.，M.D.，M.H.，R.J.C.，K.E.A.，L.D.，A.K.，S.L.，M.S.，和L.F.G。

carried out the analysis. A.T. and A.W. performed the computational studies. M.S. and L.F.G. supervised the work. G.M., R.L.P., R.K., V.I., V.K., R.P., T.H., L.D., M.S., and L.F.G. wrote the manuscript. All authors commented on the manuscript.Corresponding authorCorrespondence to.

。A、 T.和A.W.进行了计算研究。M、 S.和L.F.G.监督了这项工作。G.M.，R.L.P.，R.K.，V.I.，V.K.，R.P.，T.H.，L.D.，M.S。和L.F.G.撰写了手稿。所有作者都对稿件发表了评论。对应作者对应。

Luis F. Godinho.Ethics declarations

路易斯·戈迪尼奥。道德宣言

Competing interests

相互竞争的利益

G.M., R.L.P., R.K., V.I., R.J.S., M.M.C., V.K., R.P., A.J., J.D., T.H., W.B., G.P., K.O., D.K., A.S., C.B., R.R., C.P., T.G., A.T., A.W., M.D., D.G., M.H., R.J.C., K.E.A., L.D., A.K., S.L., M.S., and L.F.G. are or were employees of Immunocore Ltd.

G、 M.，R.L.P.，R.K.，V.I.，R.J.S.，M.M.C.，V.K.，R.P.，A.J.，J.D.，T.H.，W.B.，G.P.，K.O.，D.K.，A.S.，C.B.，R.R.，C.P.，T.G.，A.T.，A.W.，M.D.，D.G.，M.H.，R.J.C.，K.E.A.，L.D.，A.K.，S.L.，M.S.和L.F.G.是或曾经是Immunocore Ltd.的员工。

Peer review

同行评审

Peer review information

同行评审信息

Nature Communications thanks Antonio Bertoletti, Michael Birnbaum, who co-reviewed with Lucy Walters and the other anonymous reviewer(s) for their contribution to the peer review of this work. A peer review file is available.

《自然通讯》感谢安东尼奥·贝托莱蒂（AntonioBertoletti）、迈克尔·伯恩鲍姆（MichaelBirnbaum），他们与露西·沃尔特斯（LucyWalters）和其他匿名审稿人共同审稿，感谢他们对这项工作的同行评议做出的贡献。可以获得同行评议文件。

Additional informationPublisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.Supplementary informationSupplementary InformationDescription of Additional Supplementary FilesSupplementary Data 1Supplementary Data 2Reporting SummaryTransparent Peer Review fileSource dataSource DataRights and permissions.

Additional informationPublisher的注释Springer Nature在已发布的地图和机构隶属关系中的管辖权主张方面保持中立。补充信息补充信息其他补充文件的描述补充数据1补充数据2报告摘要透明的同行评审文件源数据源数据权限。

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.

开放获取本文是根据知识共享署名4.0国际许可证授权的，该许可证允许以任何媒体或格式使用，共享，改编，分发和复制，只要您对原始作者和来源给予适当的信任，提供知识共享许可证的链接，并指出是否进行了更改。

The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

本文中的图像或其他第三方材料包含在文章的知识共享许可中，除非在材料的信用额度中另有说明。如果材料未包含在文章的知识共享许可中，并且您的预期用途不受法律法规的许可或超出许可用途，则您需要直接获得版权所有者的许可。

To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/..

要查看此许可证的副本，请访问http://creativecommons.org/licenses/by/4.0/..

Reprints and permissionsAbout this articleCite this articleMurugesan, G., Paterson, R.L., Kulkarni, R. et al. Viral sequence determines HLA-E-restricted T cell recognition of hepatitis B surface antigen.

转载和许可本文引用本文Murugesan，G.，Paterson，R.L.，Kulkarni，R。等人。病毒序列决定了HLA-E限制性T细胞对乙型肝炎表面抗原的识别。

Nat Commun 15, 10126 (2024). https://doi.org/10.1038/s41467-024-54378-9Download citationReceived: 20 February 2024Accepted: 08 November 2024Published: 22 November 2024DOI: https://doi.org/10.1038/s41467-024-54378-9Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

Nat Commun 1510126（2024）。https://doi.org/10.1038/s41467-024-54378-9Download引文接收日期：2024年2月20日接受日期：2024年11月8日发布日期：2024年11月22日OI：https://doi.org/10.1038/s41467-024-54378-9Share本文与您共享以下链接的任何人都可以阅读此内容：获取可共享链接对不起，本文目前没有可共享的链接。复制到剪贴板。

Provided by the Springer Nature SharedIt content-sharing initiative

由Springer Nature SharedIt内容共享计划提供