Comprehensive Analysis of CMV pp65 Antigen-Specific CD8+ T Cell Responses According to HLA Class I Alleles and Intra-Individual Dominance

To define whether individual HLA class I alleles are used preferentially in human CMV-specific CTL responses, CD8⁺ T cell responses restricted by up to six HLA class I alleles in an individual were simultaneously measured using K562-based artificial antigen-presenting cells expressing both CMV pp65 antigen and one of 32 HLA class I alleles (7 alleles in HLA-A, 14 alleles in HLA-B, and 11 alleles in HLA-C locus) present in 50 healthy Korean donors. The CD8⁺ T cell responses to pp65 in the HLA-C locus were lower than responses to those in HLA-A and -B locus and there was no difference between the HLA-A and HLA-B loci. HLA-A*0201, -B*0702, and -C*0801 showed the highest magnitude and frequency of immune responses to pp65 at each locus. However, HLA-A*0207, -B*5901, -B*5801, -B*1511, -C*0302, and -C*0202 did not show any immune responses. Although each individual has up to six different HLA alleles, 46% of the donors showed one allele, 24% showed two alleles, and 2% showed three alleles that responded to pp65. Interestingly, the frequencies of HLA-A alleles were significantly correlated with the positivity of particular alleles. These results suggest the impact of investigating the immune response restricted by single HLA alleles, which indicates the possibility of predicting individuals with low responsiveness to CMV, required in third-party CTL therapy for partially matched recipient-donors.