title: Molecular recognition of human CD1b antigen complexes: evidence for a common pattern of interaction with alpha beta TCRs.
abstract: Ag-specific T cell recognition is mediated through direct interaction of clonotypic TCRs with complexes formed between Ag-presenting molecules and their bound ligands. Although characterized in substantial detail for class I and class II MHC encoded molecules, the molecular interactions responsible for TCR recognition of the CD1 lipid and glycolipid Ag-presenting molecules are not yet well understood. Using a panel of epitope-specific Abs and site-specific mutants of the CD1b molecule, we showed that TCR interactions occur on the membrane distal aspects of the CD1b molecule over the alpha1 and alpha2 domain helices. The location of residues on CD1b important for this interaction suggested that TCRs bind in a diagonal orientation relative to the longitudinal axes of the alpha helices. The data point to a model in which TCR interaction extends over the opening of the putative Ag-binding groove, making multiple direct contacts with both alpha helices and bound Ag. Although reminiscent of TCR interaction with MHC class I, our data also pointed to significant differences between the TCR interactions with CD1 and MHC encoded Ag-presenting molecules, indicating that Ag receptor binding must be modified to accommodate the unique molecular structure of the CD1b molecule and the unusual Ags it presents.
authors.affiliation: Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: A
authors.initials: A
authors.lastname: Melián
authors.forename: G F
authors.initials: GF
authors.lastname: Watts
authors.forename: A
authors.initials: A
authors.lastname: Shamshiev
authors.forename: G
authors.initials: G
authors.lastname: De Libero
authors.forename: A
authors.initials: A
authors.lastname: Clatworthy
authors.forename: M
authors.initials: M
authors.lastname: Vincent
authors.forename: M B
authors.initials: MB
authors.lastname: Brenner
authors.forename: S
authors.initials: S
authors.lastname: Behar
authors.forename: K
authors.initials: K
authors.lastname: Niazi
authors.forename: R L
authors.initials: RL
authors.lastname: Modlin
authors.forename: S
authors.initials: S
authors.lastname: Almo
authors.forename: D
authors.initials: D
authors.lastname: Ostrov
authors.forename: S G
authors.initials: SG
authors.lastname: Nathenson
authors.forename: S A
authors.initials: SA
authors.lastname: Porcelli
mesh_terms: D019138:Antibodies, Blocking / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017951:Antigen Presentation / Q000235:genetics; D018949:Antigens, CD1 / Q000097:blood / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D002999:Clone Cells; D006017:Glycolipids / Q000276:immunology / Q000378:metabolism; D006801:Humans; D046911:Macromolecular Substances; D008285:Major Histocompatibility Complex / Q000235:genetics / Q000276:immunology; D018448:Models, Immunological; D016297:Mutagenesis, Site-Directed; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D018949:Antigens, CD1; D006017:Glycolipids; D046911:Macromolecular Substances; D016693:Receptors, Antigen, T-Cell, alpha-beta; C048938:glucose mycolate