BETA-CHAIN BROADENS RANGE OF CD8 RECOGNITION FOR MHC CLASS-I MOLECULE

It is known that the alpha-chain of CD8 binds to a negatively charged loop composed of residues 223 to 229 on MHC class I Ag and that binding of CD8-alpha enhances Ag recognition of T cells. We have recently shown that the mouse CD8-alpha-homodimer does not bind to either the HLA class I-alpha-3 domain or a mutant of H-2K(b) Ag containing a substitution of glutamine for methionine at residue 224, which brings this residue toward the human consensus. Here we report a complementary study of the CD8 beta-chain. The functional role of the CD8 beta-chain was analyzed by using four T cell hybridoma lines expressing mouse CD8-alpha and transfected with the mouse CD8-beta gene. As compared with the lines expressing only CD8-alpha, allorecognition of the chimeric H-2K(b) Ag that contains the HLA class I alpha-3 domain was enhanced in lines expressing both CD8-alpha and -beta. This enhancement was blocked by either anti-CD8 mAb or anti-HLA class I alpha-3 domain mAb. In addition, we show that CD8-alpha-beta-binds the H-2K(b) mutant Ag at residue 224. These results suggest that the beta-chain allows the CD8-alpha-beta heterodimer to recognize the chimeric H-2K(b) Ag. A model for the role of the beta-chain is presented.