T cell receptor-MHC class I peptide interactions: affinity, kinetics, and specificity.
The critical discriminatory event in the activation of T lymphocytes bearing alpha beta T cell receptors (TCRs) is their interaction with a molecular complex consisting of a peptide bound to a major histocompatibility complex (MHC)-encoded class I or class II molecule on the surface of an antigen-presenting cell. The kinetics of binding were measured of a purified TCR to molecular complexes of a purified soluble analog of the murine MHC class I molecule H-2Ld (sH-2Ld) and a synthetic octamer peptide p2CL in a direct, real-time assay based on surface plasmon resonance. The kinetic dissociation rate of the MHC-peptide complex from the TCR was rapid (2.6 x 10(-2) second-1, corresponding to a half-time for dissociation of approximately 27 seconds), and the kinetic association rate was 2.1 x 10(5) M-1 second-1. The equilibrium constant for dissociation was approximately 10(-7) M. These values indicate that TCRs must interact with a multivalent array of MHC-peptide complexes to trigger T cell signaling.
Corr
M
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Molecular Biology Section, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892.
Slanetz
A E
AE
Boyd
L F
LF
Jelonek
M T
MT
Khilko
S
S
al-Ramadi
B K
BK
Kim
Y S
YS
Maher
S E
SE
Bothwell
A L
AL
Margulies
D H
DH
D000595:Amino Acid Sequence; D000818:Animals; D015374:Biosensing Techniques; D006183:H-2 Antigens / Q000378:metabolism*; D064532:Histocompatibility Antigen H-2D; D007700:Kinetics; D008285:Major Histocompatibility Complex; D051379:Mice; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000378:metabolism*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism*; D012995:Solubility
D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D009842:Oligopeptides; D016693:Receptors, Antigen, T-Cell, alpha-beta