A Kinetic Basis for T Cell Receptor Repertoire Selection During an Immune Response

Immunity. 1999 Apr;10(4):485-92. doi: 10.1016/s1074-7613(00)80048-5.

Abstract

The basis for T cell antigen receptor (TCR) repertoire selection upon repeated antigenic challenge is unclear. We evaluated the avidity and dissociation kinetics of peptide/major histocompatibility complex (MHC) tetramer binding to antigen-specific T lymphocytes isolated following primary or secondary immunization. The data reveal a narrowing of the secondary repertoire relative to the primary repertoire, largely resulting from the loss of cells expressing TCRs with the fastest dissociation rates for peptide/MHC binding. In addition, T cells in the secondary response express TCRs of higher average affinity for peptide/MHC than cells in the primary response. These results provide a link between the kinetics and affinity of TCR-peptide/MHC interactions and TCR sequence selection during the course of an immune response.

Publication types

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

MeSH terms

  • Animals
  • Binding Sites / immunology
  • Female
  • Immunization, Secondary
  • Kinetics
  • Ligands
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Peptides / immunology
  • Peptides / metabolism
  • Receptors, Antigen, T-Cell / biosynthesis
  • Receptors, Antigen, T-Cell / immunology*
  • Receptors, Antigen, T-Cell / metabolism*
  • Staining and Labeling
  • T-Lymphocyte Subsets / chemistry
  • T-Lymphocyte Subsets / metabolism

Substances

  • Ligands
  • Peptides
  • Receptors, Antigen, T-Cell