Regulation of CD1 Antigen-presenting Complex Stability

• Published in: The Journal of biological chemistry Vol. 285; no. 16; pp. 11937 - 11947
• Main Authors: Odyniec, Artur N., Barral, Duarte C., Garg, Salil, Tatituri, Raju V., Besra, Gurdyal S., Brenner, Michael B.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 16.04.2010; American Society for Biochemistry and Molecular Biology
• Subjects: Animals; Antigen Presentation; Antigens MHC; Antigens, CD1 - chemistry; Antigens, CD1 - genetics; Antigens, CD1 - metabolism; beta 2-Microglobulin - chemistry; beta 2-Microglobulin - metabolism; CD1; Cell Line; Cell Membrane - immunology; Cell Membrane - metabolism; Endosomes - immunology; Endosomes - metabolism; Glycolipids; HeLa Cells; Histocompatibility Antigens Class I - chemistry; Histocompatibility Antigens Class I - metabolism; Histocompatibility Antigens Class II - chemistry; Histocompatibility Antigens Class II - metabolism; Humans; Hydrogen-Ion Concentration; Immunology/Antigen; Immunology/Antigen Processing; Lipid; Lipids; Lysosomes - immunology; Lysosomes - metabolism; Mice; Multiprotein Complexes; NKT Cell; Protein Isoforms - chemistry; Protein Isoforms - genetics; Protein Isoforms - metabolism; Protein Stability; Protein Structure and Folding; Recombinant Proteins - chemistry; Recombinant Proteins - genetics; Recombinant Proteins - metabolism; Transfection; CD1; NKT Cell; Immunology/Antigen; Glycolipids; Protein/Stability; Immunology/Antigen Processing; Antigens MHC; Lipid
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M109.077933

For major histocompatibility complex class I and II molecules, the binding of specific peptide antigens is essential for assembly and trafficking and is at the center of their quality control mechanism. However, the role of lipid antigen binding in stabilization and quality control of CD1 heavy chain (HC)·β2-microglobulin (β2m) complexes is unclear. Furthermore, the distinct trafficking and loading routes of CD1 proteins take them from mildly acidic pH in early endososmal compartments (pH 6.0) to markedly acidic pH in lysosomes (pH 5.0) and back to neutral pH of the cell surface (pH 7.4). Here, we present evidence that the stability of each CD1 HC·β2m complex is determined by the distinct pH optima identical to that of the intracellular compartments in which each CD1 isoform resides. Although stable at acidic endosomal pH, complexes are only stable at cell surface pH 7.4 when bound to specific lipid antigens. The proposed model outlines a quality control program that allows lipid exchange at low endosomal pH without dissociation of the CD1 HC·β2m complex and then stabilizes the antigen-loaded complex at neutral pH at the cell surface.