Comprehensive Analysis of Epstein-Barr Virus LMP2A-Specific CD8+ and CD4+ T Cell Responses Restricted to Each HLA Class I and II Allotype Within an Individual

• Published in: Immune network Vol. 23; no. 2; pp. 92 - 107
• Main Authors: Jo, Hyeong-A, Hyun, Seung-Joo, Hyun, You-Seok, Lee, Yong-Hun, Kim, Sun-Mi, Baek, In-Cheol, Sohn, Hyun-Jung, Kim, Tai-Gyu
• Format: Journal Article
• Language: English
• Published: Korea (South) 대한면역학회 01.04.2023; The Korean Association of Immunologists
• Subjects: Original; SUP> Dominant allotype; HLA class I and II; and CD4< Intra-individual dominance; lt; Epstein-Barr virus; CD8< T cells; LMP2A; CD8+ and CD4+ T cells
• ISSN: 1598-2629; 2092-6685
• DOI: 10.4110/in.2023.23.e17

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.