Predominant Role of Amino-Terminal Sequences in Dictating Efficiency of Class II Major Histocompatibility Complex α β Dimer Expression

• Published in: Proceedings of the National Academy of Sciences - PNAS 1987-11, Vol.84 (22), p.8065-8069
• Main Authors: Sant, Andrea J., Braunstein, Ned S., Germain, Ronald N.
• Format: Article
• Language: English
• Subjects: Alleles; Animals; Antibodies; Biological Transport; Cell lines; Complementary DNA; Dimers; Gene Expression Regulation; Genes, MHC Class II; histocompatibility antigen H-2; Histocompatibility Antigens Class II - biosynthesis; Histocompatibility Antigens Class II - genetics; Ia antigen; L cells; L Cells (Cell Line); Mice; Molecular chains; Molecules; Protein Multimerization; Protein Processing, Post-Translational; Recombinant Fusion Proteins - biosynthesis; RNA; Transfection
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.84.22.8065

Cell surface expression of class II major histocompatibility complex-encoded (Ia) molecules depends on association of the component α and β chains into a stable heterodimer. In the mouse, two isotypes of class II molecules have been identified, AβAα and EβEα. However, experiments from this laboratory have shown that, following DNA-mediated gene transfer into murine L cells, an AβEα-mixed-isotype molecule can be assembled and expressed at the cell surface. In the present study, we have investigated the structural features of the β chain that control the extent of association and level of membrane expression of AβEα interisotypic pairs. The use of intact allelic Aβ genes demonstrated that only Aβd chains, but not Aβb or Aβk chains, can be coexpressed on the surface membrane with Eα chains. Transfection of recombinant Aβ genes that encode all or half of the β 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 Aβ chain completely controlled this variation in expression with Eα. Isotypically mixed β genes encoding the Aβ 1 domain of either Aβd or Aβk chains and the β 2, transmembrane, and intracytoplasmic portions of Eβ chains were used to assess the role of isotypically conserved structures in α β 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 Aα or Eα chains. These results argue strongly that variations in the efficiency with which distinct Ia α β 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.