Dominant TCR V alpha usage by virus and tumor-reactive T cells with wide affinity ranges for their specific antigens

Eur J Immunol. 2002 Nov;32(11):3181-90. doi: 10.1002/1521-4141(200211)32:11<3181::AID-IMMU3181>3.0.CO;2-2.

Abstract

We have studied the TCR features and functional responses of three sets of human cytolytic T cell (CTL) clones, recognizing antigenic peptides presented by HLA-A2 and derived from the Epstein-Barr virus proteins BMLF1 and BRLF1 and from the melanoma protein Melan-A/MART-1. Within each set, a majority of clones used a recurrent V alpha region, even though they expressed highly diverse TCR beta chains and V(D)J junctional sequences. Functional assays and peptide/MHC multimer binding studies indicated that this restricted V alpha usage was not associated with the affinity/avidity of the CTL clones. The V alpha dominance, which may be a frequent feature of antigen-specific T cells, likely reflects a restricted geometry of TCR/peptide/MHC complexes, primarily determined by V alpha CDR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antigens, Neoplasm
  • Complementarity Determining Regions
  • HLA-A2 Antigen / immunology
  • Herpesvirus 4, Human / immunology*
  • Humans
  • Immediate-Early Proteins / immunology
  • MART-1 Antigen
  • Melanoma / immunology*
  • Neoplasm Proteins / immunology
  • Phosphoproteins / immunology
  • Receptors, Antigen, T-Cell, alpha-beta / chemistry
  • Receptors, Antigen, T-Cell, alpha-beta / physiology*
  • T-Lymphocytes, Cytotoxic / immunology*
  • Trans-Activators / immunology
  • Viral Proteins*

Substances

  • Antigens, Neoplasm
  • BRLF1 protein, Human herpesvirus 4
  • Complementarity Determining Regions
  • HLA-A2 Antigen
  • Immediate-Early Proteins
  • MART-1 Antigen
  • MLANA protein, human
  • Neoplasm Proteins
  • Phosphoproteins
  • Receptors, Antigen, T-Cell, alpha-beta
  • SM protein, Human herpesvirus 4
  • Trans-Activators
  • Viral Proteins