Efficient T cell activation requires an optimal dwell-time of interaction between the TCR and the pMHC complex.
Cytotoxic T cell (CTL) activation by antigen requires the specific detection of peptide-major histocompatibility class I (pMHC) molecules on the target-cell surface by the T cell receptor (TCR). We examined the effect of mutations in the antigen-binding site of a Kb-restricted TCR on T cell activation, antigen binding and dissociation from antigen.These parameters were also examined for variants derived from a Kd-restricted peptide that was recognized by a CTL clone. Using these two independent systems, we show that T cell activation can be impaired by mutations that either decrease or increase the binding half-life of the TCR-pMHC interaction. Our data indicate that efficient T cell activation occurs within an optimal dwell-time range of TCR-pMHC interaction. This restricted dwell-time range is consistent with the exclusion of either extremely low or high affinity T cells from the expanded population during immune responses.
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
A M
AM
Kalergis
N
N
Boucheron
M A
MA
Doucey
E
E
Palmieri
E C
EC
Goyarts
Z
Z
Vegh
I F
IF
Luescher
S G
SG
Nathenson
D000818:Animals; D000941:Antigens / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D006207:Half-Life; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D006825:Hybridomas; D007700:Kinetics; D008213:Lymphocyte Activation; D016297:Mutagenesis, Site-Directed; D019251:Nucleocapsid / Q000235:genetics / Q000276:immunology; D019590:Nucleocapsid Proteins; D010455:Peptides / Q000235:genetics / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000941:Antigens; D016207:Cytokines; D015395:Histocompatibility Antigens Class I; D019590:Nucleocapsid Proteins; D010455:Peptides; D011948:Receptors, Antigen, T-Cell