HLA polymorphisms and T cell cytokine responses to processed HLA class II measles virus peptides: the rationale for a measles peptide vaccine
Abstract number: 10.1111/j.1198-743X.2004.902_o294.x
Previously we have reported that HLA-DR molecules contribute the main restriction determinants for antigen-specific T-cell recognition of naturally processed measles virus (MV) class II epitopes derived from MV phosphoprotein (MV-P) and nucleoprotein (MV-N). We demonstrated a significant association of DRB1*0301 alleles with MV-P specific IFN-g and IL-4 responses. In addition, DRB1*1501 and DRB1*1103/*1303 alleles were associated with MV-N induced IFN-g and IL-4 secretion, respectively. Because of the tight linkage disequilibrium between DR and DQ and/or DP alleles and the frequent sharing of epitopes among these HLA class II loci, the importance of non-DR class II molecules in MV peptide responses should be understood.
We studied the association between cytokine responses and DQ and DP alleles among 313 (168 males and 145 females) children aged 1218 years who received two doses of MMR-II vaccine. Genomic DNA was extracted from blood samples and used for HLA allele typing. PBMC were cultured alone or stimulated with peptides, and cytokines in supernatants were measured by ELISA. The allelic associations were determined by linear regression analysis.
Overall mean IFN-g and IL-4 secretion levels for MV-P and MV-N peptides were 99.3 compared with 13.2 pg/mL, and 0.3 compared with 4.1 pg/mL, respectively. Examination of IFN-g responses to MV-P peptide indicated that none of the alleles of the DQ locus were associated with MV-P induced T-cell response. A marginally significant increase in the frequency of the DQB1*0201 (P = 0.06) and DQB1*0603 (P = 0.10) alleles was found among subjects who demonstrated high IL-4 levels to MV-P. DPB1*0201 (P = 0.05) and DPB1*1301 (P = 0.10) alleles provided suggestive evidence of an association with MV-P induced IL-4 secretion. DQB1*0602 (P = 0.03) allele provided the evidence of an association with MV-N induced high IFN-g responses. By examining the DP alleles individually, we found a significant (P = 0.006) increase in the frequency of the DPB1* 0501 allele among subjects who produced low MV-N specific IL-4 responses.
We demonstrated that MV-derived peptides can be recognised in association with different HLA molecules, including DR, DQ and DP alleles. We suggest that non-DR class II molecules also restrict cytokine responses to naturally processed MV peptides. These results should be viewed cautiously due to multiple testing issues. This information is important for the design of new vaccines."
|Session name:||XXIst ISTH Congress|
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