Role of L3T4 and Ia in the heteroclitic response of T cells to cytochrome c.
The activation of helper T lymphocytes has been proposed to result from the sum of low-affinity interactions between the specific immune receptor, as well as nonpolymorphic receptors such as L3T4 on the T cell surface, and nominal antigen and Ia displayed in a multivalent array on the antigen-presenting cell surface. The present work takes advantage of a T cell hybridoma specific for pigeon cytochrome c in the context of I-Ek, which responds to tobacco hornworm moth cytochrome c at one hundredth the concentration of the homologous antigen, to determine if the T cell's requirement for L3T4 and Ia is directly related to its functional affinity for antigen. The results demonstrate that the T cell's activation by pigeon cytochrome c was blocked by antibodies directed to L3T4 and to I-Ek, even at antigen concentrations twofold to fourfold above those required for maximal responses. In contrast, the response to tobacco hornworm moth cytochrome c was not as affected by these antibodies under equivalent superoptimal conditions. The same phenomenon was observed for the T cell's activation by the carboxyl-terminal peptide fragments of the two cytochromes c, which do not require processing, indicating that the differences were not due to the relative efficiency of processing and/or presentation of the antigens. Although both I-Ek- and L3T4-specific antibodies blocked the T cell response to pigeon cytochrome, antibodies to I-Ak had no effect, even though I-Ak had been considered to be a ligand for L3T4. Thus, either Ia does not bind L3T4 or, if it does, I-Ek must be a sufficient ligand for L3T4 for T cells that recognize their antigen in the context of I-Ek. These studies provide more definitive evidence that the T cell's requirement for the functions of Ia and of L3T4 is dependent on the T cell's functional affinity for its antigenic determinant. This data is consistent with a model of T cell activation in which, given a high enough affinity of the T cell receptor for the processed antigen, the requirement for other components of a stimulatory complex, such as Ia and L3T4, may diminish to undetectable levels.
Lakey
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Margoliash
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Fitch
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Pierce
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D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D001666:Binding Sites, Antibody; D001667:Binding, Competitive; D010856:Columbidae; D003574:Cytochrome c Group / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D005260:Female; D006649:Histocompatibility Antigens / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D051379:Mice; D008808:Mice, Inbred CBA; D009036:Moths; D013601:T-Lymphocytes / Q000276:immunology*
D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D003574:Cytochrome c Group; D000939:Epitopes; D006649:Histocompatibility Antigens; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen