Detection of CML determinants associated with H-2 controlled E beta and E alpha chains.

The serologically detectable molecules encoded by the H-2 complex, the major histocompatibility complex (MHC) of the mouse, fall into two classes-class I and class II (ref. 1). The class I molecules encoded by the K and D loci have a molecular weight of 44,000 and are noncovalently associated with beta 2 microglobulin which is not controlled by the MHC. The class II molecules are of two kinds, A and E, each consisting of two noncovalently associated polypeptide chains, alpha (Mr approximately 34,000) and beta (Mr approximately 28,000). Three of the four chains, A alpha, A beta and E beta, are controlled by loci in the I-A subregion, whereas the locus controlling the E alpha chain is located in the I-E subregion of the H-2 complex. Thus the loci coding for the E alpha and E beta chains are separated by at least one (J) and perhaps more loci. It has been shown that the E alpha and E beta chains are synthesized independently, and that the E alpha chain is required for the insertion of the E beta chain in the plasma membrane. We demonstrate here that the E alpha E beta complex (the E molecule) can evoke in vitro cell-mediated lymphocytotoxicity (CML) without previous sensitization in vivo, and that the strong CML reactivity is directed against allele-specific determinants on the highly polymorphic E beta chain.