Differences in SARS-CoV-2-specific immune responses have been observed between individuals following natural infection or vaccination. In addition to already known factors, such as age, sex, COVID-19 severity, comorbidity, vaccination status, hybrid immunity, and duration of infection, inter-individual variations in SARS-CoV-2 immune responses may, in part, be explained by structural differences brought about by genetic variation in the human leukocyte antigen (HLA) molecules responsible for the presentation of SARS-CoV-2 antigens to T effector cells. While dendritic cells present peptides with HLA class I molecules to CD8+ T cells to induce cytotoxic T lymphocyte responses (CTLs), they present peptides with HLA class II molecules to T follicular helper cells to induce B cell differentiation followed by memory B cell and plasma cell maturation. Plasma cells then produce SARS-CoV-2-specific antibodies. Here, we review published data linking HLA genetic variation or polymorphisms with differences in SARS-CoV-2-specific antibody responses. While there is evidence that heterogeneity in antibody response might be related to HLA variation, there are conflicting findings due in part to differences in study designs. We provide insight into why more research is needed in this area. Elucidating the genetic basis of variability in the SARS-CoV-2 immune response will help to optimize diagnostic tools and lead to the development of new vaccines and therapeutics against SARS-CoV-2 and other infectious diseases.
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机译:在自然感染或接种疫苗后的个体之间观察到 SARS-CoV-2 特异性免疫反应的差异。除了年龄、性别、COVID-19 严重程度、合并症、疫苗接种状态、混合免疫和感染持续时间等已知因素外,SARS-CoV-2 免疫反应的个体间差异可能部分解释为负责将 SARS-CoV-2 抗原呈递给 T 效应细胞的人类白细胞抗原 (HLA) 分子的遗传变异带来的结构差异。树突状细胞将带有 HLA I 类分子的肽呈递给 CD8+ T 细胞以诱导细胞毒性 T 淋巴细胞反应 (CTL),而树突状细胞将带有 HLA II 类分子的肽呈递给 T 滤泡辅助细胞以诱导 B 细胞分化,然后是记忆 B 细胞和浆细胞成熟。然后浆细胞产生 SARS-CoV-2 特异性抗体。在这里,我们回顾了已发表的数据,将 HLA 遗传变异或多态性与 SARS-CoV-2 特异性抗体反应的差异联系起来。虽然有证据表明抗体反应的异质性可能与 HLA 变异有关,但部分由于研究设计的差异,存在相互矛盾的结果。我们提供了关于为什么该领域需要更多研究的见解。阐明 SARS-CoV-2 免疫反应变异的遗传基础将有助于优化诊断工具,并导致针对 SARS-CoV-2 和其他传染病的新疫苗和疗法的开发。
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