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

J Immunol. 2000 Apr 15;164(8):4244-9. doi: 10.4049/jimmunol.164.8.4244.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Antigens, Viral / immunology*
  • Clone Cells
  • Epitopes, T-Lymphocyte / blood*
  • HLA-DQ Antigens / blood*
  • HLA-DQ Antigens / genetics
  • HLA-DQ Antigens / immunology
  • Herpes Genitalis / blood
  • Herpes Genitalis / immunology*
  • Herpes Simplex Virus Protein Vmw65 / immunology
  • Herpes Simplex Virus Protein Vmw65 / metabolism
  • Herpesvirus 2, Human / immunology*
  • Humans
  • Immunodominant Epitopes / blood*
  • Influenza A virus / immunology
  • Lymphocyte Count
  • Molecular Sequence Data
  • Peptide Fragments / immunology
  • Peptide Fragments / metabolism
  • Protein Binding / immunology
  • Stem Cells / immunology
  • Stem Cells / metabolism
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism

Substances

  • Antigens, Viral
  • Epitopes, T-Lymphocyte
  • HLA-DQ Antigens
  • Herpes Simplex Virus Protein Vmw65
  • Immunodominant Epitopes
  • Peptide Fragments