IN-VIVO DIMERIC ASSOCIATION OF CLASS-I MHC HEAVY-CHAINS - POSSIBLE RELATIONSHIP TO CLASS-I MHC HEAVY CHAIN-BETA(2)-MICROGLOBULIN DISSOCIATION

Class I MHC molecules have been thought to occur in vivo both as class I MHC heavy chain-beta2-m heterodimers, which are or are not associat ed with antigenic peptide, and as free class I MHC heavy chains. Class I MHC molecules are now found also to occur in another type of struct ure: a heavy chain-heavy chain dimer. Biochemical studies show that he avy chain dimers are disulfide-linked via a conserved cytoplasmic doma in cysteine. H-2L(d), H-2D(b), and H-2D(d) class I dimers fail to reac t with certain alpha1 and alpha2 domain-specific antibodies. Furthermo re, although beta2-m-specific antibodies coprecipitate class I MHC hea vy chains, they do not coprecipitate class I MHC heavy chain dimers. P ulse-chase studies show that heavy chain dimer formation occurs at dif ferent points in the biosynthesis of class I MHC molecules in beta2-m and beta2-m- Cells: in beta2-m+ cells, heavy chain dimers form after the class I molecules have traversed the medial Golgi cisternae, where as in beta2-m- cells they form immediately. Culturing of beta2-m+ cell s with exogenous beta2-m prevents the formation of H-2L(d)/D(b) heavy chain dimers. We conclude that dimer formation occurs as a consequence of loss or unavailability of beta2-m. Class I MHC heavy chain dimeriz ation may provide a mechanism for removal of immunologically dysfuncti onal molecules.