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 (Mr ∼34,000) and β (Mr ∼28,000)2,3. Three of the four chains, A α, Aβ and Eβ, 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 Eα and Eβ chains are separated by at least one (J) and perhaps more loci3,4. It has been shown that the Eα and Eβ chains are synthesized independently, and that the Eα chain is required for the insertion of the Eβ chain in the plasma membrane 4. We demonstrate here that the EαEβ 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 Eβ chain.
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