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: Inna G Ovsyannikova, Robert A Vierkant, Gregory A Poland
• Journal: Vaccine (Vaccine) Vol. 24 Issue 25 Pg. 5381-9 (Jun 19 2006) ISSN: 0264-410X [Print] Netherlands
• PMID: 16714073 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Cytokines
• HLA-DP Antigens
• HLA-DQ Antigens
• HLA-DQ beta-Chains
• HLA-DQB1 antigen
• HLA-DR Antigens
• HLA-DRB1 Chains
• HLA-DRB1*03:01 antigen
• Measles-Mumps-Rubella Vaccine
• Peptides
• Interleukin-4
• Interferon-gamma

Topics

• Adolescent
• Alleles
• Amino Acid Sequence
• Child
• Cytokines (metabolism)
• Female
• HLA-DP Antigens (genetics)
• HLA-DQ Antigens (genetics)
• HLA-DQ beta-Chains
• HLA-DR Antigens (chemistry, genetics, metabolism)
• HLA-DRB1 Chains
• Humans
• Interferon-gamma (metabolism)
• Interleukin-4 (metabolism)
• Male
• Measles virus (chemistry, immunology)
• Measles-Mumps-Rubella Vaccine (administration & dosage, immunology)
• Molecular Sequence Data
• Peptides (chemistry, immunology, metabolism)
• Polymorphism, Genetic