The T-cell accessory molecule CD4 recognizes a monomorphic determinant on isolated Ia.
The membrane protein CD4 is commonly found on mature T cells specific for antigen in association with class II major histocompatibility complex (MHC; Ia) proteins. This correlation has led to the suggestion that CD4 binds to a monomorphic region of the Ia molecule on the antigen-presenting cell (APC) and functions either by enhancing interaction between the T cell and the APC, or conversely, by transducing negative signals to the T cell. To address this hypothesis, we have made use of sublines from an unusual T hybrid that is class I MHC restricted but also CD4+. By incorporating purified MHC proteins into a planar membrane system, we show that different Ia molecules can greatly enhance the ability of a CD4+ but not a CD4- variant of this class I-restricted T hybrid to respond to isolated class I molecules. T-cell responses can be strongly augmented by the concurrent expression of CD4 on the T cell and any of four different Ia proteins on planar membranes, thus supporting the idea that CD4 binds to a monomorphic region of the Ia molecule and increases the avidity with which the T cell can interact with its target.
Gay
D
D
Department of Microbiology, University of Colorado Health Sciences Center, Denver 80262.
Buus
S
S
Pasternak
J
J
Kappler
J
J
Marrack
P
P
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D002462:Cell Membrane / Q000276:immunology; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006825:Hybridomas; D008024:Ligands; D008081:Liposomes; D008863:Microspheres; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000648:ultrastructure
D000945:Antigens, Differentiation, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; D008024:Ligands; D008081:Liposomes; D011948:Receptors, Antigen, T-Cell