Quantitative analysis of the contribution of TCR/pepMHC affinity and CD8 to T cell activation.
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.
Holler
Phillip D
PD
Department of Biochemistry, University of Illinois, Urbana, IL 61801, USA.
Kranz
David M
DM
D000818:Animals; D016827:CD8 Antigens / Q000235:genetics / Q000378:metabolism*; D006183:H-2 Antigens / Q000378:metabolism; D064532:Histocompatibility Antigen H-2D; D006825:Hybridomas / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D010455:Peptides / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection
D016827:CD8 Antigens; D006183:H-2 Antigens; C024755:H-2K(K) antigen; D064532:Histocompatibility Antigen H-2D; D010455:Peptides; D016693:Receptors, Antigen, T-Cell, alpha-beta