Influence of HLA-DRB1 alleles on lymphoproliferative responses to a naturally processed and presented measles virus phosphoprotein in measles immunized individuals.

Abstract

Identification of stimulatory T-cell epitopes recognized by CD4+ T lymphocytes is important for vaccine development. Our previous studies using mass spectrometry identified a naturally processed HLA class II restricted DRB1*0301 T cell epitope in the measles virus phosphoprotein, MV-P1 (residues 179-197). Here we provide lymphocyte proliferation data from peripheral blood mononuclear cells (PBMC) obtained from 131 HLA-DRB1*0301-positive and HLA-DRB1*0301-negative (HLA discordant) individuals previously immunized against measles and report that a single amino acid substitution in the MV-P1 T cell epitope can reduce T cell proliferation and CD4+ T-cell recognition. Measles virus and measles peptide-specific lymphoproliferative responses and HLA-DRB1 allele associations reveal that the DRB1*0701 allele provided suggestive evidence of association with both measles virus (p = 0.03) and MV-P1 peptide (p = 0.06) lymphoproliferation. A marginally significant increase in the frequency of the *0301 allele (p = 0.10) was found among subjects who demonstrated low cellular responses to the measles virus. We found no associations between proliferation levels to the MV-P1 and MV-P2 peptides with *0301 alleles. We speculate that the glutamic acid at position 192 of the measles phosphoprotein is a critical immunogenicity factor and may influence the antigenicity of the naturally processed HLA class II MV-P1 epitope.

• Authors: Inna G Ovsyannikova, Gregory A Poland, Nathan J Easler, Robert A Vierkant
• Journal: Human immunology (Hum Immunol) Vol. 65 Issue 3 Pg. 209-17 (Mar 2004) ISSN: 0198-8859 [Print] United States
• PMID: 15041159 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Epitopes, T-Lymphocyte
• HLA-DR Antigens
• HLA-DRB1 Chains
• HLA-DRB1*03:01 antigen
• Measles Vaccine
• Phosphoproteins

Topics

• Alleles
• Amino Acid Substitution (genetics)
• Antigen Presentation (immunology)
• CD4-Positive T-Lymphocytes (immunology)
• Cell Division (immunology)
• Epitopes, T-Lymphocyte (immunology)
• HLA-DR Antigens (genetics, immunology)
• HLA-DRB1 Chains
• Humans
• Measles Vaccine
• Measles virus (metabolism)
• Phosphoproteins (immunology)