Virus infection expands a biased subset of T cells that bind tetrameric class I peptide complexes

Eur J Immunol. 2003 Jun;33(6):1557-67. doi: 10.1002/eji.200323715.

Abstract

We have used a TCR beta-chain transgenic mouse to examine the relationship between the ability of a T cell to bind soluble class I-peptide complexes and its response to antigenic stimulation in vivo. T cells from gBT-I.3beta TCR beta-chain transgenic mice preferentially carried TCR alpha-chains bearing the same Valpha2 V region as found in the parent receptor specific for an immunodominant HSV-1 gB-peptide. Furthermore, CD8(+) T cells from these mice bound K(b)-gB tetrameric complexes with relatively high frequency, and most of these cells contained a Valpha2 TCR alpha-chain. Detailed sequence analysis of the tetramer-binding peripheral T cells showed that this was a heterogenous population expressing TCR with only partial sequence similarity to the parent receptor, which took the form of preferential inclusion of the parental Jalpha16 element. Infection with HSV-1, however, selected a subset of tetramer-positive T cells. This was based on the emergence of a co-dominant Jalpha usage and selection of a restricted CDR3alpha length. Therefore, the ability to bind soluble MHC-peptide complexes does not always correlate with the ability of a T cell to respond to its cognate antigen after in vivo stimulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antigens, Viral / immunology*
  • Antigens, Viral / metabolism
  • Biopolymers
  • Complementarity Determining Regions / genetics
  • Epitopes, T-Lymphocyte / immunology*
  • Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor*
  • Gene Rearrangement, beta-Chain T-Cell Antigen Receptor
  • Genes, T-Cell Receptor alpha*
  • Genes, T-Cell Receptor beta*
  • H-2 Antigens / immunology*
  • H-2 Antigens / metabolism
  • Herpes Simplex / immunology*
  • Immunodominant Epitopes / immunology*
  • Lymphocyte Activation*
  • Macromolecular Substances
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Peptide Fragments / immunology*
  • Peptide Fragments / metabolism
  • Receptors, Antigen, T-Cell, alpha-beta / genetics*
  • Simplexvirus / immunology*
  • Specific Pathogen-Free Organisms
  • T-Lymphocyte Subsets / immunology*
  • Thymus Gland / immunology
  • Viral Envelope Proteins / immunology*
  • Viral Envelope Proteins / metabolism

Substances

  • Antigens, Viral
  • Biopolymers
  • Complementarity Determining Regions
  • Epitopes, T-Lymphocyte
  • H-2 Antigens
  • H-2Kb protein, mouse
  • Immunodominant Epitopes
  • Macromolecular Substances
  • Peptide Fragments
  • Receptors, Antigen, T-Cell, alpha-beta
  • Viral Envelope Proteins
  • glycoprotein B, Simplexvirus