Importance of HLA-DQ and HLA-DP polymorphisms in cytokine responses to naturally processed HLA-DR-derived measles virus peptides

Abstract

We studied the association between class II human leukocyte antigen (HLA)-DRB1*0301 presented measles virus (MV) peptide-specific cytokine responses and DQB1 and DPB1 alleles among 313 individuals who received two doses of measles–mumps–rubella-II vaccine. The overall median IFN-γ secretion levels (first and third quartiles) for the 19-amino acid MV phosphoprotein (MV-P)- and 14-amino acid MV nucleoprotein (MV-N)-derived peptides were 27.7 pg/ml (1.8, 109.4) and 1.9 pg/ml (−6.2, 13.0), respectively; median IL-4 secretion levels were −0.6 pg/ml (−7.1, 6.2) and 2.4 pg/ml (−3.2, 9.3), respectively. Primary statistical analyses were adjusted for previously identified DRB1 associations. A marginally significant increase in the frequency of the DQB1*0604 ( p = 0.02) allele was found among subjects who demonstrated detectable IL-4 levels to the MV-P peptide. Further, DPB1*0201 ( p = 0.02) and DPB1*1301 ( p = 0.09) alleles provided suggestive evidence of an association with MV-P-induced IL-4 secretion. Examination of IFN-γ responses to MV-P and MV-N indicated that none of the individual alleles of the DQB1 and DPB1 loci were associated with peptide-induced T cell response. An increase in the frequency of DPB1*0501 ( p = 0.01) was found among subjects who failed to produce MV-N peptide-specific IL-4 responses. These data further confirm that HLA-DRB1 alleles are the major restriction molecules for MV-P and MV-N measles virus antigen presentation to T cells. We speculate that MV-P and MV-N peptides derived from DRB1*0301 could potentially be recognized in association with different HLA molecules, including DQB1 and DPB1; however, statistical adjustments for the effect of HLA-DR locus could potentially alter these genetic relationships. This concept provides important information supporting the use of promiscuous peptides in a peptide-based vaccine approach.