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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

  • Hyeong-A Jo (Department of Microbiology, College of Medicine, The Catholic University of Korea) ;
  • Seung-Joo Hyun (Department of Microbiology, College of Medicine, The Catholic University of Korea) ;
  • You-Seok Hyun (Department of Microbiology, College of Medicine, The Catholic University of Korea) ;
  • Yong-Hun Lee (Department of Microbiology, College of Medicine, The Catholic University of Korea) ;
  • Sun-Mi Kim (Hematopoietic Stem Cell Bank, College of Medicine, The Catholic University of Korea) ;
  • In-Cheol Baek (Hematopoietic Stem Cell Bank, College of Medicine, The Catholic University of Korea) ;
  • Hyun-Jung Sohn (Hematopoietic Stem Cell Bank, College of Medicine, The Catholic University of Korea) ;
  • Tai-Gyu Kim (Department of Microbiology, College of Medicine, The Catholic University of Korea)
  • Received : 2022.08.05
  • Accepted : 2022.11.02
  • Published : 2023.04.30
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Abstract

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)/5×105 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.

Keywords

Acknowledgement

We thank the Catholic Hematopoietic Stem Cell Bank, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea, for typing HLA.

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