PREFERENTIAL PRESENTATION OF HERPES-SIMPLEX VIRUS T-CELL ANTIGEN BY HLA DQA1-ASTERISK-0501 DQB1-ASTERISK-0201 IN COMPARISON TO HLA DQA1-ASTERISK-0201/DQB1-ASTERISK-0201/

The HLA DQA1 locus is polymorphic. Haplotypes containing HLA DQA10501 , but not HLA DQA10201, together with HLA DQB1*0201 are associated wi th Grave's disease and celiac sprue. In this report, we demonstrate a functional correlate of DQA1 polymorphism. T cells infiltrating a herp es simplex virus (HSV) lesion from a HLA DQ 2,7 individual yielded a v irus-specific CD4+ clone restricted by DQ2. Presentation of viral pept ide and protein segregated with DQA1 allele, because cell lines bearin g DQA10501/DQB1*0201 heterodimers presented antigen in proliferation and cytotoxicity assays much more efficiently than cell lines bearing DQA10201/DQB1*0201. Binding of viral peptide to cell lines bearing DQ A10201, in comparison to DQA1*0501, was only moderately reduced and m ay not explain this effect. Truncation and substitution analyses of pe ptide binding and T-cell activation were performed to determine which viral peptide residues contacting TCR might therefore be presented in an altered conformation by DQA10201/DQB1*0201. Residues 432, 435, 437 , 438, and 440 (position P1, P4, P6, P7, and P9) contributed to DQ2 bi nding, whereas residues 431, 433, 434, and 436 (positions P-1, P2, P3, and P5) contributed to TCR contact. Differential presentation of pept ide by HLA DQ2 heterodimers varying at the DQA1 locus may have relevan ce to host defense and the pathogenesis of HLA DQ2-associated autoimmu ne diseases. (C) American Society for Histocompatibility and Immunogen etics, 1997.