Predominant role of amino-terminal sequences in dictating efficiency of class II major histocompatibility complex alpha beta dimer expression.
- 1 November 1987
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 84 (22) , 8065-8069
- https://doi.org/10.1073/pnas.84.22.8065
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.This publication has 28 references indexed in Scilit:
- Structure-function analysis of the Abm12 beta mutation using site-directed mutagenesis and DNA-mediated gene transfer.The Journal of Immunology, 1987
- Allele-specific control of Ia molecule surface expression and conformation: implications for a general model of Ia structure-function relationships.Proceedings of the National Academy of Sciences, 1987
- The Relation Between Major Histocompatibility Complex (MHC) Restriction and the Capacity of Ia to Bind Immunogenic PeptidesScience, 1987
- Isolation and characterization of antigen-la complexes involved in T cell recognitionCell, 1986
- Efficient cell surface expression of class II MHC molecules in the absence of associated invariant chain.The Journal of Experimental Medicine, 1986
- Alternative protein products with different carboxyl termini from a single class I gene, H-2Kb.Proceedings of the National Academy of Sciences, 1986
- Unexpected expression of a unique mixed-isotype class II MHC molecule by transfected L-cellsNature, 1986
- Influence of allelic polymorphism on the assembly and surface expression of class II MHC (Ia) moleculesCell, 1985
- "Exon-shuffling" maps control of antibody- and T-cell-recognition sites to the NH2-terminal domain of the class II major histocompatibility polypeptide A beta.Proceedings of the National Academy of Sciences, 1985
- An Improved Method for Isolation of H-2 and Ia Alloantigens with Immunoprecipitation Induced by Protein A-Bearing StaphylococciThe Journal of Immunology, 1976