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HLA-DQ Tetramers Identify Epitope-Specific T Cells in Peripheral Blood of Herpes Simplex Virus Type 2-Infected Individuals: Direct Detection of Immunodominant

By Antigen-responsive Cells, Gerald T. Nepom, Sigrid N. Reymond and David M. Koelle


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 MHCpeptide 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 369–380 peptide has a lower binding affinity for DQ0602 molecules 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. The HLA class II molecules, DR, DQ, and DP, act as restriction elements for presentation of antigenic peptides to human CD4 � T cells. Techniques of T cell cloning and limiting dilution assays have been successfully applied to the detectio

Year: 2013
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