title: 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-gamma 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-gamma 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.
authors.affiliation: Mayo Vaccine Research Group, Guggenheim 611C, 200 First Street SW, Rochester, MN 55905, USA.
authors.forename: Inna G
authors.initials: IG
authors.lastname: Ovsyannikova
authors.forename: Robert A
authors.initials: RA
authors.lastname: Vierkant
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Poland
mesh_terms: D000293:Adolescent; D000483:Alleles; D000595:Amino Acid Sequence; D002648:Child; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006682:HLA-DP Antigens / Q000235:genetics*; D006683:HLA-DQ Antigens / Q000235:genetics*; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D059811:HLA-DRB1 Chains; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008297:Male; D008459:Measles virus / Q000737:chemistry / Q000276:immunology*; D022542:Measles-Mumps-Rubella Vaccine / Q000008:administration & dosage / Q000276:immunology; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D011110:Polymorphism, Genetic
chemical_list: D016207:Cytokines; D006682:HLA-DP Antigens; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553502:HLA-DRB1*03:01 antigen; D022542:Measles-Mumps-Rubella Vaccine; D010455:Peptides; D015847:Interleukin-4; D007371:Interferon-gamma