Functional supertype of HLA-A2 in the presentation of Flu matrix p58-66 to induce CD8+ T-cell response in a Northern Chinese population

: The functional supertype of HLA‐A2 was investigated in the presentation of the A*0201‐restricted Flu matrix p58–66 peptide to activate recall CD8+ T‐cell response. In healthy Northern Chinese, the HLA‐A2 supertype was mainly composed of the six alleles, A*0201 (26.4%), A*0206 (12.7%), A*0203 (8.2%), A*0207 (7.3%), A*0210 (1.8%) and A*0205 (0.9%), as analyzed by PCR using sequence specific primer (PCR‐SSP) and sequence based typing (SBT) . The IFN‐γ release Elispot assay was employed to assess effector CD8+ T cells. In A*0201‐bearing individuals, the CD8+ T‐cell response was potent when stimulated with autologous CD8– PBMCs. The frequency of the effector CD8+ T cells was 96.6% with the magnitude of effector CD8+ T cells of 225 SFC/5 × 104 CD8+ T cells and the RI of 25.7. In non‐A*0201 individuals, the effector CD8+ T cells were minimally detectable while the peptide was presented by the autologous CD8– PBMCs. However, the induction of the response of CD8+ T cells obtained from non‐A*0201 individuals was remarkably improved when the peptide was presented by autologous dendritic cells instead of CD8– PBMCs. The HLA‐A2 alleles possessing cross‐reactivity in the peptide presentation were mainly of A*0206 and non‐A*0201 heterozygotes of A*0206 and A*0210. Moreover, A*0206 as the HLA‐A2 functional supertype was further confirmed by tetramer assay. In two A*0206+ donors with CD8+ T‐cell response to the peptide, the CD8+ T‐cell frequency assessed by specific binding of peptide HLA‐A*0201 tetramer was 4.62% and 1.66%, respectively. Thus, our results have substantiated the immunological relevance of the HLA‐A2 supertype, which may benefit the design of peptide vaccines with the potential to be applicable in broader populations.