Role of Transmembrane Domain Interactions in the Assembly of Class II MHC Molecules

• Published in: Science (American Association for the Advancement of Science) 1992-10, Vol.258 (5082), p.659-662
• Main Authors: Cosson, Pierre, Bonifacino, Juan S.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Antibodies; Antigens; Biological and medical sciences; CD4 antigen; CD8 antigen; Cell Line; Cellular immunity; Cellular metabolism; Chimeras; clonal selection; Cloning, Molecular; COS cells; differentiation; DNA Mutational Analysis; Endoplasmic Reticulum - metabolism; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Glycine - metabolism; Histocompatibility antigens (hla, h-2 and other systems); Histocompatibility Antigens Class II - biosynthesis; Histocompatibility Antigens Class II - chemistry; Histocompatibility Antigens Class II - genetics; lymphocytes T; Major histocompatibility complex; Mice; Microscopy; Molecular immunology; Molecular interactions; Molecular Sequence Data; Molecules; negative; Physiological aspects; Protein Conformation; Protein structure; Proteins; Receptors, Interleukin-2 - biosynthesis; Receptors, Interleukin-2 - chemistry; Receptors, Interleukin-2 - genetics; Recombinant Fusion Proteins - biosynthesis; Recombinant Fusion Proteins - chemistry; Recombinant Fusion Proteins - genetics; Structure; T lymphocytes; thymocytes
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1329208

Evidence is presented that suggests a role for transmembrane domain interactions in the assembly of class II major histocompatibility complex (MHC) molecules. Mutations in the transmembrane domains of the class II MHC α or β chains resulted in proteins that did not generate complexes recognized by conformation-dependent antibodies and that were largely retained in the endoplasmic reticulum. Insertion of the α and β transmembrane domains into other proteins allowed the chimeric proteins to assemble, suggesting a direct interaction of the α and β transmembrane domains. The interactions were mediated by a structural motif involving several glycine residues on the same face of a putative α helix.