Alterations in CD4 dependence accompany T cell development and differentiation.
Several studies have indicated that the necessity for co-receptor engagement during T cell activation depends on the avidity of the TCR-MHC interaction under investigation. Using thymocytes, naive T cells and a long-term T cell line isolated from 2B4 TCR transgenic mice, we have examined the role of the CD4 co-receptor on cells expressing the identical TCR at multiple stages of T cell maturation. When anti-CD4 Fab fragments were used to block CD4-MHC class II interactions, we found decreasing CD4 dependence as T cells matured. As a second approach to examining the role of the CD4 co-receptor, we generated I-Ek mutants defective in CD4 interactions. In the course of this study, we identified a new potential site for CD4 interaction in the beta1 domain of I-Ek. The new beta1 mutation and a mutation in the previously described CD4 binding site in the beta2 domain both interfere with stimulation of 2B4 thymocytes, but not mature T cells. Together these data demonstrate that the role of the CD4 co-receptor depends on the state of maturation of the T cell.
Yelon
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Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA.
Spain
L M
LM
Lim
K
K
Berg
L J
LJ
D000818:Animals; D015704:CD4 Antigens / Q000235:genetics* / Q000276:immunology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000276:immunology*; D011485:Protein Binding / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D015704:CD4 Antigens; D000949:Histocompatibility Antigens Class II; D007140:Immunoglobulin Fab Fragments; D011948:Receptors, Antigen, T-Cell