Comprehensive Analysis of Cytomegalovirus pp65 Antigen-Specific CD8 + T Cell Responses According to Human Leukocyte Antigen Class I Allotypes and Intraindividual Dominance

• Published in: Frontiers in immunology 2017-11, Vol.8, p.1591-1591
• Main Authors: Hyun, Seung-Joo, Sohn, Hyun-Jung, Lee, Hyun-Joo, Lee, Seon-Duk, Kim, Sueon, Sohn, Dae-Hee, Hong, Cheol-Hwa, Choi, Haeyoun, Cho, Hyun-Il, Kim, Tai-Gyu
• Format: Article
• Language: English
• Subjects: CD8+ T cell; cytomegalovirus pp65; human leukocyte antigen class I; human leukocyte antigen restriction; immunodominant pattern; Immunology; preferential usage
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2017.01591

To define whether individual human leukocyte antigen (HLA) class I allotypes are used preferentially in human cytomegalovirus (CMV)-specific cytotoxic T lymphocyte responses, CD8 T cell responses restricted by up to six HLA class I allotypes in an individual were measured in parallel using K562-based artificial antigen-presenting cells expressing both CMV pp65 antigen and one of 32 HLA class I allotypes (7 HLA-A, 14 HLA-B, and 11 HLA-C) present in 50 healthy Korean donors. The CD8 T cell responses to pp65 in the HLA-C allotypes were lower than responses to those in HLA-A and -B allotypes and there was no difference between the HLA-A and HLA-B loci. HLA-A*02:01, -B*07:02, and -C*08:01 showed the highest magnitude and frequency of immune responses to pp65 at each HLA class I locus. However, HLA-A*02:07, -B*59:01, -B*58:01, -B*15:11, -C*03:02, and -C*02:02 did not show any immune responses. Although each individual has up to six different HLA allotypes, 46% of the donors showed one allotype, 24% showed two allotypes, and 2% showed three allotypes that responded to pp65. Interestingly, the frequencies of HLA-A alleles were significantly correlated with the positivity of specific allotypes. Our results demonstrate that specific HLA class I allotypes are preferentially used in the CD8 T cell immune response to pp65 and that a hierarchy among HLA class I allotypes is present in an individual.