title: Molecular Analysis of Lipid-Reactive Vδ1 γδ T Cells Identified by CD1c Tetramers.
abstract: CD1c is abundantly expressed on human dendritic cells (DC) and B cells, where it binds and displays lipid Ags to T cells. In this study, we report that CD1c tetramers carrying Mycobacterium tuberculosis phosphomycoketide bind γδ TCRs. An unbiased method of ligand-based TCR selection detects interactions only with Vδ1(+) TCRs, and mutational analyses demonstrate a role of the Vδ1 domain during recognition. These results strengthen evidence for a role of CD1c in the γδ T cell response, providing biophysical evidence for CD1c-γδ TCR interactions and a named foreign Ag. Surprisingly, TCRs also bind CD1c complexes formed with diverse lipids such as lysophosphatidylcholine, sulfatide, or mannosyl-phosophomycoketide, but not lipopeptide ligands. Dissection of TCR interactions with CD1c carrying foreign Ags, permissive ligands, and nonpermissive lipid ligands clarifies the molecular basis of the frequently observed but poorly understood phenomenon of mixed self- and foreign Ag reactivity in the CD1 system.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637;
authors.forename: Sobhan
authors.identifier: http://orcid.org/0000-0003-3511-7869
authors.initials: S
authors.lastname: Roy
authors.affiliation: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA 02115; Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada;
authors.forename: Dalam
authors.identifier: http://orcid.org/0000-0002-1177-0225
authors.initials: D
authors.lastname: Ly
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637; Committee on Immunology, University of Chicago, Chicago, IL 60637;
authors.forename: Caitlin D
authors.initials: CD
authors.lastname: Castro
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637;
authors.forename: Nan-Sheng
authors.initials: NS
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637; Department of Pathology, University of Chicago, Chicago, IL 60637;
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Hawk
authors.affiliation: Department of Microbiology and Immunology, Emory Vaccine Center at Yerkes, Emory University School of Medicine, Atlanta, GA 30329; and.
authors.forename: John D
authors.initials: JD
authors.lastname: Altman
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637; Department of Pathology, University of Chicago, Chicago, IL 60637;
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Meredith
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637; Department of Chemistry, University of Chicago, Chicago, IL 60637.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Piccirilli
authors.affiliation: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA 02115; ejadams@uchicago.edu bmoody@partners.org.
authors.forename: D Branch
authors.identifier: http://orcid.org/0000-0003-2306-3058
authors.initials: DB
authors.lastname: Moody
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637; Committee on Immunology, University of Chicago, Chicago, IL 60637; ejadams@uchicago.edu bmoody@partners.org.
authors.forename: Erin J
authors.initials: EJ
authors.lastname: Adams
mesh_terms: D017951:Antigen Presentation / Q000276:immunology*; D018949:Antigens, CD1 / Q000276:immunology*; D005434:Flow Cytometry; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology*; D016133:Polymerase Chain Reaction; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014161:Transduction, Genetic
chemical_list: D018949:Antigens, CD1; C437944:CD1C protein, human; D006023:Glycoproteins; D008024:Ligands; D016692:Receptors, Antigen, T-Cell, gamma-delta