Molecular Interaction of CD1b with Lipoglycan Antigens

• Published in: Immunity (Cambridge, Mass.) Vol. 8; no. 3; pp. 331 - 340
• Main Authors: Ernst, William A, Maher, Juli, Cho, Sungae, Niazi, Kayvan R, Chatterjee, Delphi, Moody, D.Branch, Besra, Gurdyal S, Watanabe, Yutaka, Jensen, Peter E, Porcelli, Steven A, Kronenberg, Mitchell, Modlin, Robert L
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.1998
• Subjects: Anilino Naphthalenesulfonates; Antigen Presentation; Antigens, Bacterial - immunology; Antigens, CD1 - immunology; beta 2-Microglobulin - immunology; Glycolipids - immunology; Hydrogen-Ion Concentration; Lipopolysaccharides - immunology; Mycobacterium leprae - immunology; Phosphatidylinositols - immunology; Protein Conformation; Recombinant Proteins - immunology; Spectrometry, Fluorescence
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/S1074-7613(00)80538-5

The ability of human CD1b molecules to present nonpeptide antigens is suggested by the T cell recognition of microbial lipids and lipoglycans in the presence of CD1b-expressing antigen-presenting cells. We demonstrate the high-affinity interaction of CD1b molecules with the acyl side chains of known T cell antigens, lipoarabinomannan, phosphatidylinositol mannoside, and glucose monomycolate. Furthermore, CD1b–antigen binding was optimal at acidic pH, consistent with the known requirement for endosomal acidification in CD1b-restricted antigen presentation. The mechanism for CD1b–ligand interaction involves the partial unfolding of the α helices of CD1b at acidic pH, revealing a hydrophobic binding site that could accommodate lipid. These data provide direct evidence that the CD1b molecule has evolved unique biochemical properties that enable the binding of lipid-containing antigens from intracellular pathogens.