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 A0201-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, A0201 (26.4%), A0206 (12.7%), A0203 (8.2%), A0207 (7.3%), A0210 (1.8%) and A0205 (0.9%), as analyzed by PCR using sequence specific primer (PCR-SSP) and sequence based typing (SBT). The IFN-gamma release Elispot assay was employed to assess effector CD8+ T cells. In A0201-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 x 104 CD8+ T cells and the RI of 25.7. In non-A0201 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-A0201 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 A0206 and non-A0201 heterozygotes of A0206 and A0210. Moreover, A0206 as the HLA-A2 functional supertype was further confirmed by tetramer assay. In two A0206+ 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.