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*
Virginia Mason Research Center, Seattle, WA 98101;
R. H. Williams Laboratory and Molecular and Cellular Biology Program and
Department of Immunology, University of Washington, Seattle, WA 98195; and
§
Virology Division, Harborview Medical Center, Seattle, WA 98104
Ag-specific CD4+ T cells are present in peripheral blood in low frequency, where they undergo recruitment and expansion during immune responses and in the pathogenesis of numerous autoimmune diseases. MHC tetramers, which constitute a labeled MHC-peptide ligand suitable for binding to the Ag-specific receptor on T cells, provide a novel approach for the detection and characterization of such rare cells. In this study, we utilized this technology to identify HLA DQ-restricted Ag-specific T cells in the peripheral blood of human subjects and to identify immunodominant epitopes associated with viral infection. Peptides representing potential epitope regions of the VP16 protein from HSV-2 were loaded onto recombinant DQ0602 molecules to generate a panel of Ag-specific DQ0602 tetramers. VP16 Ag-specific DQ-restricted T cells were identified and expanded from the peripheral blood of HSV-2-infected individuals, representing two predominant epitope specificities. Although the VP16 369380 peptide has a lower binding affinity for DQ0602 molecules than the VP16 3352 peptide, T cells that recognized the VP16 369380 peptide occurred at a much higher frequency than those that were specific for the VP16 3352 peptide.
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