A region of conformational variability outside the peptide-binding site ofa class I MHC molecule

Peptide binding is known to influence the conformation of the surface of cl ass I molecules as detected with mAbs and TCR. A new conformationally sensi tive epitope on the mouse class I molecule K-b is defined by mAb AF6-88.5. The recognized structure is affected by amino acid substitutions in any of the three external domains of the class I heavy chain and, in addition, is influenced by the substitution of human for mouse beta(2)-microglobulin. In terestingly, the epitope for this Ab is not affected by mutations within th e peptide-binding cleft or by the nature of the peptide bound, These findin gs indicate that the effect of a change in one domain of class I can radiat e to other parts of the molecule. Furthermore, the existence of conformatio nally sensitive structures outside of the peptide-binding site suggests the possibility that class I molecules may change their structure in response to binding by receptors and ligands such as the TCR and the coligand CD8. S uch structural changes may represent signals that can influence cellular ac tivation events.