Antigen recognition by the T cell receptor is enhanced by CD8 alpha-chain binding to the alpha 3 domain of MHC class I molecules, not by signaling via the cytoplasmic domain of CD8 alpha.
The binding specificities and function of mouse CD8 were studied using a CD4-CD8- allospecific T cell hybridoma, chimeric class I MHC molecules, and a CD8 alpha deletion mutant. By transfecting the mouse CD8 alpha gene into a IL-2 producing, H-2Kb specific hybridoma, IL-2 production was increased when L cells expressing Kb were used as stimulators. However, no increase in IL-2 was observed when a KbKbB7 hybrid molecule, composed of the alpha 1 and alpha 2 domains of H-2Kb, and the alpha 3 domain of HLA-B7, was used as a stimulator. Comparison between T cell hybridomas that expressed full-length CD8 alpha and a deletion mutant lacking part of the cytoplasmic domain revealed identical responsiveness for H-2Kb. The data suggest that the mouse CD8 alpha homodimer does not bind to the alpha 3 domain of HLA class I molecules and that CD8 alpha acts as a co-receptor with the TCR by binding the same MHC molecule for alloantigen recognition. Our data also provide evidence that CD8 alpha signal transduction through its cytoplasmic tail by association with p56lck is not an absolute requirement for antigen recognition by T cells.
Tanabe
M
M
Department of Immunology, University of Tokyo, Japan.
Karaki
S
S
Takiguchi
M
M
Nakauchi
H
H
D000818:Animals; D015152:Blotting, Northern; D016827:CD8 Antigens / Q000276:immunology; D006183:H-2 Antigens / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006825:Hybridomas / Q000276:immunology; D007156:Immunologic Memory; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D014162:Transfection
D016827:CD8 Antigens; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D015395:Histocompatibility Antigens Class I; D007375:Interleukin-1; D011948:Receptors, Antigen, T-Cell