Discovery of a monoclonal, high-affinity CD8+ T-cell clone following natural hepatitis C virus infection

IF 3.2 4区 医学 Q3 CELL BIOLOGY Immunology & Cell Biology Pub Date : 2024-06-10 DOI:10.1111/imcb.12791
Curtis Cai, Elizabeth Keoshkerian, Kristof Wing, Jerome Samir, Manuel Effenberger, Kilian Schober, Rowena A Bull, Andrew R Lloyd, Dirk H Busch, Fabio Luciani
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Abstract

CD8+ T cells recognizing their cognate antigen are typically recruited as a polyclonal population consisting of multiple clonotypes with varying T-cell receptor (TCR) affinity to the target peptide–major histocompatibility complex (pMHC) complex. Advances in single-cell sequencing have increased accessibility toward identifying TCRs with matched antigens. Here we present the discovery of a monoclonal CD8+ T-cell population with specificity for a hepatitis C virus (HCV)–derived human leukocyte antigen (HLA) class I epitope (HLA-B*07:02 GPRLGVRAT) which was isolated directly ex vivo from an individual with an episode of acutely resolved HCV infection. This population was absent before infection and underwent expansion and stable maintenance for at least 2 years after infection as measured by HLA-multimer staining. Furthermore, the monoclonal clonotype was characterized by an unusually long dissociation time (half-life = 794 s and koff = 5.73 × 10−4) for its target antigen when compared with previously published results. A comparison with related populations of HCV-specific populations derived from the same individual and a second individual suggested that high-affinity TCR–pMHC interactions may be inherent to epitope identity and shape the phenotype of responses which has implications for rational TCR selection and design in the age of personalized immunotherapies.

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发现自然感染丙型肝炎病毒后的单克隆高亲和性 CD8+ T 细胞克隆。
识别其同源抗原的 CD8+ T 细胞通常是作为多克隆群体被招募的,该群体由多个克隆型组成,其 T 细胞受体(TCR)与目标肽-主要组织相容性复合物(pMHC)复合物的亲和力各不相同。单细胞测序技术的进步增加了识别具有匹配抗原的 TCR 的可能性。在这里,我们发现了一个对丙型肝炎病毒(HCV)衍生的人类白细胞抗原(HLA)I类表位(HLA-B*07:02 GPRLGVRAT)具有特异性的单克隆CD8+T细胞群,该细胞群是直接从急性HCV感染者体内分离出来的。根据 HLA-多聚酶染色法的测定,该群体在感染前并不存在,但在感染后至少 2 年内不断扩大并稳定维持。此外,与之前发表的结果相比,该单克隆克隆型的特点是其目标抗原的解离时间异常长(半衰期 = 794 秒,koff = 5.73 × 10-4)。与来自同一个人和第二个人的相关 HCV 特异性群体的比较表明,高亲和性 TCR 与 PMHC 的相互作用可能是表位特征的固有特性,并塑造了反应的表型,这对个性化免疫疗法时代的合理 TCR 选择和设计具有重要意义。
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来源期刊
Immunology & Cell Biology
Immunology & Cell Biology 医学-免疫学
CiteScore
7.50
自引率
2.50%
发文量
98
审稿时长
4-8 weeks
期刊介绍: The Australasian Society for Immunology Incorporated (ASI) was created by the amalgamation in 1991 of the Australian Society for Immunology, formed in 1970, and the New Zealand Society for Immunology, formed in 1975. The aim of the Society is to encourage and support the discipline of immunology in the Australasian region. It is a broadly based Society, embracing clinical and experimental, cellular and molecular immunology in humans and animals. The Society provides a network for the exchange of information and for collaboration within Australia, New Zealand and overseas. ASI members have been prominent in advancing biological and medical research worldwide. We seek to encourage the study of immunology in Australia and New Zealand and are active in introducing young scientists to the discipline.
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