Functional analysis of the interaction of the antigen-specific T cell receptor with its ligands.
Increasing the number of antigen-specific T cell clones in a T cell proliferation assay resulted in a shift in the antigen dose-response curves toward higher amounts of antigen (i.e., more antigen was required to achieve a given degree of stimulation). The antigen dose-response curve shifts were found to reflect the competition that occurred between the antigen-specific T cell receptors for their ligand, a combination of antigen and Ia molecule. This observation made it possible to determine whether the difference in the potency with which several synthetic cytochrome c analogs could stimulate one cytochrome c-specific T cell clone was due to a difference in the avidity of the antigen-specific receptors on the T cell clone for the different Ia molecule-antigen combinations. It was demonstrated that a single amino acid substitution at position 103 (which greatly diminished the potency of the analog) did not significantly alter the avidity of the T cell antigen-specific receptor for its ligand. In contrast, a substitution at position 99 (which resulted in a comparable decrease in potency) caused a dramatic loss of avidity. These results are consistent with the previous designation of residue 99 as one site on the antigen that contacts the T cell antigen-specific receptor, and of residue 103 as one part of the antigen that contacts the Ia molecule.
Ashwell
J D
JD
Fox
B S
BS
Schwartz
R H
RH
D000818:Animals; D001667:Binding, Competitive; D003574:Cytochrome c Group / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D000939:Epitopes / Q000276:immunology*; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006825:Hybridomas / Q000276:immunology / Q000378:metabolism; D007376:Interleukin-2 / Q000096:biosynthesis; D007958:Leukocyte Count; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D016685:Mitomycin; D008937:Mitomycins / Q000276:immunology; D010455:Peptides / Q000276:immunology; D011108:Polymers; D011948:Receptors, Antigen, T-Cell / Q000032:analysis* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
D003574:Cytochrome c Group; D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D008937:Mitomycins; D010455:Peptides; D011108:Polymers; D011948:Receptors, Antigen, T-Cell; C020749:GAT; D016685:Mitomycin