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.

Human Leukocyte Antigens and Cellular Immune Responses to Anthrax Vaccine Adsorbed

“…Our statistical approach and the description of the statistical analyses and methods are nearly identical to what we have previously published (16,(18)(19)(20)(21)(22). Data were descriptively summarized using frequencies and percentages for all categorical variables and medians and interquartile ranges (IQR) for all continuous variables.…”

HLA-DR specific monoclonal antibodies block lymphoproliferative response to measles vaccine in vitro: A pilot study

“…Fresh PBMCs from donors were used to optimize many variables including incubation times, antigen concentrations, and technique according to relevant findings in the literature [1,8,4]. Briefly, peripheral blood mononuclear cells (PBMC) were isolated from healthy donors within one hour of collection using standard Ficoll-Paque ™ procedures.…”

Measles

“…This is in concordance with other studies showing that certain HLA class I and II type alleles were associated with antibody [54] or CMI responses [55] following MCV. More research focusing on components of the measles virus that generate CMI responses in individuals with a specific HLA type have been undertaken [56]. In contrast, a Brazilian study showed a high rate of secondary vaccine failures that may be due to the use of different vaccines or oversensitivity of the test used to detect the nature of vaccine failure [57].…”