Cutting edge: inhibitory effects of CD4 and CD8 on T cell activation induced by high-affinity noncognate ligands.
It has been proposed that MHC restriction during thymocyte selection is controlled by coreceptor (CD4 or CD8) sequestration of the signaling molecule Lck. We explored this model as a mechanism for preventing peripheral T cell activation due to non-MHC ligand cross-reactivities of TCRs. TCRs that have a range of affinities for a class I MHC ligand were transduced into a T cell hybridoma in the absence or presence of coreceptors. High and intermediate affinity TCRs (K(D) = 17 and 540 nM) did not require CD8 for T cell activity, but CD4 acted as a potent inhibitor of the intermediate affinity TCR. These and other findings support the view that even high-affinity TCR:ligand interactions can be influenced by coreceptor sequestration of Lck. Thus, CD4 and CD8 act as "coreceptor inhibitors" to maintain appropriate TCR-mediated MHC restriction in peripheral T cell activity.
Chervin
Adam S
AS
Department of Biochemistry, University of Illinois, Urbana, IL 61801, USA.
Stone
Jennifer D
JD
Bowerman
Natalie A
NA
Kranz
David M
DM
D000818:Animals; D017951:Antigen Presentation; D015704:CD4 Antigens / Q000378:metabolism / Q000502:physiology*; D016827:CD8 Antigens / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D006183:H-2 Antigens / Q000276:immunology / Q000378:metabolism; D006825:Hybridomas; D007108:Immune Tolerance; D007166:Immunosuppressive Agents / Q000378:metabolism; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology*; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011485:Protein Binding / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism*
D015704:CD4 Antigens; D016827:CD8 Antigens; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D007166:Immunosuppressive Agents; D008024:Ligands; D011948:Receptors, Antigen, T-Cell; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)