A kinetic intermediate in the reaction of an antigenic peptide and I-Ek.
Helper T cells are triggered by molecular complexes of antigenic peptides and cell surface glycoproteins of the MHC (gene products of the major histocompatibility complex) on antigen-presenting cells. There is now a lot of evidence that the complexes between isolated class II MHC molecules and selected peptides have long half-lives of approximately one day. The reported equilibrium binding constants between antigenic peptides and class II MHC molecules however, are only micromolar, suggesting that the association rate constants are very low. The only reported association rate constant is for a chicken ovalbumin peptide (OVA323-339) binding to I-Ad, and is indeed remarkably low, about 1 litre per mole per second. Prompted by these unusual data, we have used the pigeon cytochrome-c peptide pCytc(88-104) and I-E reconstituted in planar lipid bilayers on glass slides to investigate further the kinetics of peptide-MHC reactions. We report the formation of two IEk-pCytc peptide complexes. One complex has slow apparent association and dissociation kinetics, very similar to those reported previously for the chicken ovalbumin peptide and I-Ad. The second complex forms and dissociates about a hundred times more rapidly. The short-lived complex shows peptide-MHC specificity and is a kinetic intermediate in the formation of the long-lived complex; the long-lived complex is recognized by specific T-helper cells.
Sadegh-Nasseri
S
S
Stauffer Laboratory of Physical Chemistry, Department of Chemistry, Stanford University, California 94305.
McConnell
H M
HM
D000818:Animals; D000937:Antigen-Antibody Reactions; D000941:Antigens; D010856:Columbidae; D003574:Cytochrome c Group / Q000276:immunology*; D005802:Genes, MHC Class II; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006825:Hybridomas / Q000276:immunology; D007700:Kinetics; D008051:Lipid Bilayers; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D000941:Antigens; D003574:Cytochrome c Group; D000949:Histocompatibility Antigens Class II; D008051:Lipid Bilayers