title: Predominant role of amino-terminal sequences in dictating efficiency of class II major histocompatibility complex alpha beta dimer expression.
abstract: Cell surface expression of class II major histocompatibility complex-encoded (Ia) molecules depends on association of the component alpha and beta chains into a stable heterodimer. In the mouse, two isotypes of class II molecules have been identified, A beta A alpha and E beta E alpha. However, experiments from this laboratory have shown that, following DNA-mediated gene transfer into murine L cells, an A beta E alpha-mixed-isotype molecule can be assembled and expressed at the cell surface. In the present study, we have investigated the structural features of the beta chain that control the extent of association and level of membrane expression of A beta E alpha interisotypic pairs. The use of intact allelic A beta genes demonstrated that only A beta d chains, but not A beta b or A beta k chains, can be coexpressed on the surface membrane with E alpha chains. Transfection of recombinant A beta genes that encode all or half of the beta 1 domain from one allele and the rest of the chain from another allele revealed that the 5-7 polymorphic residues in the amino-terminal 50 residues of the A beta chain completely controlled this variation in expression with E alpha. Isotypically mixed beta genes encoding the A beta 1 domain of either A beta d or A beta k chains and the beta 2, transmembrane, and intracytoplasmic portions of E beta chains were used to assess the role of isotypically conserved structures in alpha beta pairing and expression. In marked contrast to the major alterations in expression accompanying changes in the amino-terminal polymorphic residues, exchange of these carboxyl-terminal isotypic segments had no detectable influence on the efficiency of expression with either A alpha or E alpha chains. These results argue strongly that variations in the efficiency with which distinct Ia alpha beta dimers assemble and are transported to the membrane is determined almost exclusively by a critical chain interaction involving the amino-terminal domains of the molecules.
mesh_terms: D000483:Alleles; D000818:Animals; D001692:Biological Transport; D005786:Gene Expression Regulation; D005802:Genes, MHC Class II; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis* / Q000235:genetics; D007739:L Cells; D051379:Mice; D055503:Protein Multimerization; D011499:Protein Processing, Post-Translational; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D014162:Transfection
chemical_list: D000949:Histocompatibility Antigens Class II; D011993:Recombinant Fusion Proteins