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-beta 2-m heterodimers, which are or are not associated 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 structure: a heavy chain-heavy chain dimer. Biochemical studies show that heavy chain dimers are disulfide-linked via a conserved cytoplasmic domain cysteine. H-2Ld, H-2Db, and H-2Dd class I dimers fail to react with certain alpha 1 and alpha 2 domain-specific antibodies. Furthermore, although beta 2-m-specific antibodies coprecipitate class I MHC heavy chains, they do not coprecipitate class I MHC heavy chain dimers. Pulse-chase studies show that heavy chain dimer formation occurs at different points in the biosynthesis of class I MHC molecules in beta 2-m+ and beta 2-m- cells: in beta 2-m+ cells, heavy chain dimers form after the class I molecules have traversed the medial Golgi cisternae, whereas in beta 2-m- cells they form immediately. Culturing of beta 2-m+ cells with exogenous beta 2-m prevents the formation of H-2Ld/Db heavy chain dimers. We conclude that dimer formation occurs as a consequence of loss or unavailability of beta 2-m. Class I MHC heavy chain dimerization may provide a mechanism for removal of immunologically dysfunctional molecules.
Capps
G G
GG
Department of Biology, Sinsheimer Laboratories, University of California, Santa Cruz 95064.
Robinson
B E
BE
Lewis
K D
KD
Zúñiga
M C
MC
D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens / Q000378:metabolism; D003593:Cytoplasm / Q000648:ultrastructure; D004220:Disulfides; D006183:H-2 Antigens / Q000737:chemistry*; D046911:Macromolecular Substances; D051379:Mice; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010455:Peptides / Q000378:metabolism; D011485:Protein Binding; D014162:Transfection; D001613:beta 2-Microglobulin / Q000378:metabolism
D000941:Antigens; D004220:Disulfides; D006183:H-2 Antigens; D046911:Macromolecular Substances; D010455:Peptides; D001613:beta 2-Microglobulin