HLA-DQ tetramers identify epitope-specific T cells in peripheral blood of herpes simplex virus type 2-infected individuals: Direct detection of immunodominant antigen-responsive cells

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 c onstitute a labeled MHC-peptide ligand suitable for binding to the Ag-speci fic receptor on T cells, provide a novel approach for the detection and cha racterization of such rare cells. In this study, we utilized this technolog y 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 VP1 6 protein from HSV-2 were loaded onto recombinant DQ0602 molecules to gener ate 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-in fected individuals, representing two predominant epitope specificities, Alt hough the VP16 369-380 peptide has a lower binding affinity for DQ0602 mole cules than the VP16 33-52 peptide, T cells that recognized the VP16 369-380 peptide occurred at a much higher frequency than those that were specific for the VP16 33-52 peptide. The Journal of Immunology, 2000, 164: 4244-4249 .