T cell receptor (TCR)-mediated repertoire selection and loss of TCR vbeta diversity during the initiation of a CD4(+) T cell response in vivo

J Exp Med. 2000 Dec 18;192(12):1719-30. doi: 10.1084/jem.192.12.1719.

Abstract

We recently described a novel way to isolate populations of antigen-reactive CD4(+) T cells with a wide range of reactivity to a specific antigen, using immunization with a fixed dose of nominal antigen and FACS((R)) sorting by CD4(high) expression. Phenotypic, FACS((R)), functional, antibody inhibition, and major histocompatibility complex-peptide tetramer analyses, as well as T cell receptor Vbeta sequence analyses, of the antigen-specific CD4(high) T cell populations demonstrated that a diverse sperm whale myoglobin 110-121-reactive CD4(+) T cell repertoire was activated at the beginning (day 3 after immunization) of the immune response. Within 6 d of immunization, lower affinity clones were lost from the responding population, leaving an expanded population of oligoclonal, intermediate affinity (and residual high affinity) T cells. This T cell subset persisted for at least 4 wk after immunization and dominated the secondary immune response. These data provide evidence that CD4(+) T cell repertoire selection occurs early in the immune response in vivo and suggest that persistence and expansion of a population of oligoclonal, intermediate affinity T cells is involved in CD4(+) T cell memory.

Publication types

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

MeSH terms

  • Animals
  • Antigens / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Clone Cells / immunology
  • Complementarity Determining Regions / genetics*
  • Complementarity Determining Regions / immunology
  • Flow Cytometry
  • Immunization
  • Immunologic Memory / immunology
  • Kinetics
  • Lymphocyte Activation*
  • Lymphocyte Subsets / immunology
  • Lymphocyte Subsets / metabolism
  • Mice
  • Mice, Inbred DBA
  • Myoglobin / immunology
  • Peptide Fragments / immunology
  • Receptors, Antigen, T-Cell / genetics*
  • Receptors, Antigen, T-Cell / immunology*
  • Sequence Analysis

Substances

  • Antigens
  • Complementarity Determining Regions
  • Myoglobin
  • Peptide Fragments
  • Receptors, Antigen, T-Cell