title: 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.
abstract: 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 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.
authors.affiliation: Virginia Mason Research Center, Seattle, WA 98101, USA. bkwok@vmresearch.org
authors.forename: W W
authors.initials: WW
authors.lastname: Kwok
authors.forename: A W
authors.initials: AW
authors.lastname: Liu
authors.forename: E J
authors.initials: EJ
authors.lastname: Novak
authors.forename: J A
authors.initials: JA
authors.lastname: Gebe
authors.forename: R A
authors.initials: RA
authors.lastname: Ettinger
authors.forename: G T
authors.initials: GT
authors.lastname: Nepom
authors.forename: S N
authors.initials: SN
authors.lastname: Reymond
authors.forename: D M
authors.initials: DM
authors.lastname: Koelle
mesh_terms: D000595:Amino Acid Sequence; D000956:Antigens, Viral / Q000276:immunology*; D002999:Clone Cells; D018984:Epitopes, T-Lymphocyte / Q000097:blood*; D006683:HLA-DQ Antigens / Q000097:blood* / Q000235:genetics / Q000276:immunology; D006558:Herpes Genitalis / Q000097:blood / Q000276:immunology*; D017405:Herpes Simplex Virus Protein Vmw65 / Q000276:immunology / Q000378:metabolism; D018258:Herpesvirus 2, Human / Q000276:immunology*; D006801:Humans; D016056:Immunodominant Epitopes / Q000097:blood*; D009980:Influenza A virus / Q000276:immunology; D018655:Lymphocyte Count; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D013234:Stem Cells / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; D006683:HLA-DQ Antigens; D017405:Herpes Simplex Virus Protein Vmw65; D016056:Immunodominant Epitopes; D010446:Peptide Fragments