Distinct T cell interactions with HLA class II tetramers characterize a spectrum of TCR affinities in the human antigen-specific T cell response

J Immunol. 2000 Dec 15;165(12):6994-8. doi: 10.4049/jimmunol.165.12.6994.

Abstract

The polyclonal nature of T cells expanding in an ongoing immune response results in a range of disparate affinities and activation potential. Recently developed human class II tetramers provide a means to analyze this diversity by direct characterization of the trimolecular TCR-peptide-MHC interaction in live cells. Two HSV-2 VP16(369-379)-specific, DQA1*0102/DQB1*0602 (DQ0602)-restricted T cell clones were compared by means of T cell proliferation assay and HLA-DQ0602 tetramer staining. These two clones were obtained from the same subject, but show different TCR gene usage. Clone 48 was 10-fold more sensitive to VP16(369-379) peptide stimulation than clone 5 as assayed by proliferation assays, correlating with differences in MHC tetramer binding. Clone 48 gave positive staining with the DQ0602/VP16(369-379) tetramer at either 23 or 37 degrees C. Weak staining was also observed at 4 degrees C. Clone 5 showed weaker staining compared with clone 48 at 37 degrees C, and no staining was observed at 23 degrees C or on ice. Receptor internalization was not required for positive staining. Competitive binding indicates that the cell surface TCR of clone 48 has higher affinity for the DQ0602/VP16(369-379) complex than clone 5. The higher binding affinity of clone 48 for the peptide-MHC complex also correlates with a slower dissociation rate compared with clone 5.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Antigen Presentation
  • Cell Communication / immunology*
  • Cell Line
  • Clone Cells
  • Epitopes, T-Lymphocyte / immunology
  • Epitopes, T-Lymphocyte / metabolism*
  • HLA-DQ Antigens / immunology
  • HLA-DQ Antigens / metabolism*
  • Herpes Simplex Virus Protein Vmw65 / metabolism
  • Herpesvirus 2, Human / immunology
  • Humans
  • Lymphocyte Activation
  • Membrane Fluidity / immunology
  • Molecular Sequence Data
  • Peptide Fragments / immunology
  • Peptide Fragments / metabolism
  • Protein Binding / immunology
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Antigen, T-Cell / metabolism*
  • Sensitivity and Specificity
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism*

Substances

  • Epitopes, T-Lymphocyte
  • HLA-DQ Antigens
  • Herpes Simplex Virus Protein Vmw65
  • Peptide Fragments
  • Receptors, Antigen, T-Cell