Quantitative analysis of the contribution of TCR/pepMHC affinity and CD8 to T cell activation

Immunity. 2003 Feb;18(2):255-64. doi: 10.1016/s1074-7613(03)00019-0.


The relative roles of CD8, TCR:pepMHC affinity, and TCR:pepMHC dissociation rate in T cell activation have remained controversial. To determine the relationships among these factors, we used T cells transfected with normal and in vitro engineered alphabeta TCRs, in the presence or absence of CD8. The TCRs exhibited a wide range of affinities (K(D) values of 80 microM to 5 nM). T cells with the highest affinity TCRs were efficiently stimulated by peptide, with or without CD8. In contrast, CD8 was required for T cells that expressed TCRs with affinities typical of syngeneic reactions (K(D) values above approximately 3 microM). The results suggest that virtually all normal syngeneic interactions require CD8, which enhances peptide sensitivity by one million-fold or more.

Publication types

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

MeSH terms

  • Animals
  • CD8 Antigens / genetics
  • CD8 Antigens / metabolism*
  • H-2 Antigens / metabolism
  • Histocompatibility Antigen H-2D
  • Hybridomas / immunology
  • Lymphocyte Activation
  • Mice
  • Peptides / immunology
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Receptors, Antigen, T-Cell, alpha-beta / metabolism*
  • T-Lymphocytes, Cytotoxic / immunology*
  • Transfection


  • CD8 Antigens
  • H-2 Antigens
  • H-2K(K) antigen
  • Histocompatibility Antigen H-2D
  • Peptides
  • Receptors, Antigen, T-Cell, alpha-beta