AN ALTERNATIVE VIEW OF T-CELL RECEPTOR-MHC INTERACTION - T-CELL RECEPTOR BINDS TRANSVERSALLY TO THE ALPHA-HELICES OF THE MHC MOLECULE

We have attempted to elucidate the relative orientation of the T-cell receptor (TCR) to the major histocompatibility complex (MHC)-antigen c omplex during antigen recognition, using the T-cell response of B10.A (I-E(k)) and B10.A(5R) (I-E(b)) mice to the 1-23(H) peptide derived fr om glycoprotein D of the herpes simplex virus. The 1-23(H)-specific T- cells derived from both B10.A and B10.A(5R) mice use the same set of V alpha genes and a different array of V beta genes. The CDR1s of these TCR beta chains share residues at particular positions. The CDR2s of the TCR beta chains have a negative charge, which correlates with I-E( b) reactivity and with the positively charged polymorphic residues res iding at the C-terminal end of the alpha-helix of the I-E(b) beta chai n of the class II molecule. Taken together, the data suggest that the TCR beta chain interacts with both the alpha and beta chains of the MH C class II molecule, as does the TCR alpha chain.