Jo Hyeong-A, Hyun Seung-Joo, Hyun You-Seok, Lee Yong-Hun, Kim Sun-Mi, Baek In-Cheol, Sohn Hyun-Jung, Kim Tai-Gyu
Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.
Department of Biomedicine and Health Sciences, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.
Immune Netw. 2022 Dec 2;23(2):e17. doi: 10.4110/in.2023.23.e17. eCollection 2023 Apr.
Latent membrane protein 2A (LMP2A), a latent Ag commonly expressed in Epstein-Barr virus (EBV)-infected host cells, is a target for adoptive T cell therapy in EBV-associated malignancies. To define whether individual human leukocyte antigen (HLA) allotypes are used preferentially in EBV-specific T lymphocyte responses, LMP2A-specific CD8 and CD4 T cell responses in 50 healthy donors were analyzed by ELISPOT assay using artificial Ag-presenting cells expressing a single allotype. CD8 T cell responses were significantly higher than CD4 T cell responses. CD8 T cell responses were ranked from highest to lowest in the order HLA-A, HLA-B, and HLA-C loci, and CD4 T cell responses were ranked in the order HLA-DR, HLA-DP, and HLA-DQ loci. Among the 32 HLA class I and 56 HLA class II allotypes, 6 HLA-A, 7 HLA-B, 5 HLA-C, 10 HLA-DR, 2 HLA-DQ, and 2 HLA-DP allotypes showed T cell responses higher than 50 spot-forming cells (SFCs)/5×10 CD8 or CD4 T cells. Twenty-nine donors (58%) showed a high T cell response to at least one allotype of HLA class I or class II, and 4 donors (8%) had a high response to both HLA class I and class II allotypes. Interestingly, we observed an inverse correlation between the proportion of LMP2A-specific T cell responses and the frequency of HLA class I and II allotypes. These data demonstrate the allele dominance of LMP2A-specific T cell responses among HLA allotypes and their intra-individual dominance in response to only a few allotypes in an individual, which may provide useful information for genetic, pathogenic, and immunotherapeutic approaches to EBV-associated diseases.
潜伏膜蛋白2A（LMP2A）是一种通常在爱泼斯坦-巴尔病毒（EBV）感染的宿主细胞中表达的潜伏性抗原，是EBV相关恶性肿瘤过继性T细胞治疗的靶点。为了确定个体人类白细胞抗原（HLA）同种异型是否在EBV特异性T淋巴细胞反应中被优先利用，使用表达单一同种异型的人工抗原呈递细胞，通过ELISPOT测定法分析了50名健康供体中LMP2A特异性CD8和CD4 T细胞反应。CD8 T细胞反应显著高于CD4 T细胞反应。CD8 T细胞反应按HLA-A、HLA-B和HLA-C位点从高到低排序，CD4 T细胞反应按HLA-DR、HLA-DP和HLA-DQ位点排序。在32种HLA I类和56种HLA II类同种异型中，6种HLA-A、7种HLA-B、5种HLA-C、10种HLA-DR、2种HLA-DQ和2种HLA-DP同种异型显示出高于50个斑点形成细胞（SFC）/5×10 CD8或CD4 T细胞的T细胞反应。29名供体（58%）对至少一种HLA I类或II类同种异型表现出高T细胞反应，4名供体（8%）对HLA I类和II类同种异型均表现出高反应。有趣的是，我们观察到LMP2A特异性T细胞反应的比例与HLA I类和II类同种异型的频率之间呈负相关。这些数据证明了LMP2A特异性T细胞反应在HLA同种异型中的等位基因优势及其在个体中仅对少数同种异型反应的个体内优势，这可能为EBV相关疾病的遗传、致病和免疫治疗方法提供有用信息。
