Detection of CML determinants associated with H–2 controlled E_β and E_αchains

Abstract

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 β₂ 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, α (M_r ∼34,000) and β (M_r ∼28,000)^2,3. Three of the four chains, A_α, A_β and E_β, are controlled by loci in the I-A subregion, whereas the locus controlling the E_α chain is located in the I-A subregion of the H–2 complex. Thus the loci coding for the E_α and E_β chains are separated by at least one (J) and perhaps more loci^3,4. It has been shown that the E_α and E_β chains are synthesized independently, and that the E_α chain is required for the insertion of the E_β chain in the plasma membrane⁴. We demonstrate here that the E_αE_β 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_β chain.