Schmidt Katja G, Geißler Paulina, Schuster Ev-Marie, Schülein Christine, Harrer Ellen G, Schönau Verena, Luber Markus, Spriewald Bernd, Steininger Philipp, Bergmann Silke, Ensser Armin, Schober Kilian, Nganou-Makamdop Krystelle, Harrer Thomas
Infectious Diseases and Immunodeficiency Section, Department of Medicine 3, Rheumatology and Immunology, Friedrich-Alexander-Universität Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany.
Mikrobiologisches Institut - Klinische Mikrobiologie, Immunologie und Hygiene, Friedrich-Alexander-Universität Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany.
iScience. 2025 Feb 3;28(3):111949. doi: 10.1016/j.isci.2025.111949. eCollection 2025 Mar 21.
Cross-reactive T cell immunity between common cold coronaviruses and SARS-CoV-2 may influence COVID-19 susceptibility. To identify cross-reactive CD8 T cell epitopes, we analyzed responses to 21 homologous SARS-CoV-2 replicase peptides in 177 people living with HIV (PLWH) on antiretroviral therapy, of which 133 did not have prior SARS-CoV-2 infection. Replicase peptides induced IFN-γ responses in 63% of the SARS-CoV-2-naïve individuals and in 73% of individuals with prior SARS-CoV-2-infection. We could define several cross-reactive epitopes, including the HLA-B∗35:03 restricted CoV-YL8, and characterized a CoV-YL8-specific T cell receptor cloned from a SARS-CoV-2 seronegative individual. Analysis of the association between HLA-I alleles and SARS-CoV-2 infections over a 16-months period revealed that in a cohort of 452 PLWH, HLA-B∗35:03 and C∗07 were underrepresented in the 55 persons with a history of SARS-CoV-2 infection while HLA-B∗35:01 and HLA-C∗04 were associated with a higher infection rate. Taken together, our study suggests an HLA-I-mediated effect of common cold coronaviruses on SARS-CoV-2 immunity.
普通感冒冠状病毒与严重急性呼吸综合征冠状病毒2（SARS-CoV-2）之间的交叉反应性T细胞免疫可能会影响新冠病毒疾病（COVID-19）的易感性。为了确定交叉反应性CD8 T细胞表位，我们分析了177名接受抗逆转录病毒治疗的艾滋病毒感染者（PLWH）对21种同源SARS-CoV-2复制酶肽的反应，其中133人既往没有SARS-CoV-2感染。复制酶肽在63%的未感染SARS-CoV-2个体和73%的既往感染过SARS-CoV-2的个体中诱导了γ干扰素反应。我们可以确定几个交叉反应性表位，包括HLA-B∗35:03限制性的CoV-YL8，并对从一名SARS-CoV-2血清阴性个体克隆的CoV-YL8特异性T细胞受体进行了表征。对452名PLWH在16个月期间HLA-I等位基因与SARS-CoV-2感染之间关联的分析显示，在有SARS-CoV-2感染史的55人中，HLA-B∗35:03和C∗07的比例较低，而HLA-B∗35:01和HLA-C∗04与较高的感染率相关。综上所述，我们的研究表明普通感冒冠状病毒通过HLA-I对SARS-CoV-2免疫产生影响。
