title: CD1b tetramers bind αβ T cell receptors to identify a mycobacterial glycolipid-reactive T cell repertoire in humans.
abstract: Microbial lipids activate T cells by binding directly to CD1 and T cell receptors (TCRs) or by indirect effects on antigen-presenting cells involving induction of lipid autoantigens, CD1 transcription, or cytokine release. To distinguish among direct and indirect mechanisms, we developed fluorescent human CD1b tetramers and measured T cell staining. CD1b tetramer staining of T cells requires glucose monomycolate (GMM) antigens, is specific for TCR structure, and is blocked by a recombinant clonotypic TCR comprised of TRAV17 and TRBV4-1, proving that CD1b-glycolipid complexes bind the TCR. GMM-loaded tetramers brightly stain a small subpopulation of blood-derived cells from humans infected with Mycobacterium tuberculosis, providing direct detection of a CD1b-reactive T cell repertoire. Polyclonal T cells from patients sorted with tetramers are activated by GMM antigens presented by CD1b. Whereas prior studies emphasized CD8(+) and CD4(-)CD8(-) CD1b-restricted clones, CD1b tetramer-based studies show that nearly all cells express the CD4 co-receptor. These findings prove a cognate mechanism whereby CD1b-glycolipid complexes bind to TCRs. CD1b tetramers detect a natural CD1b-restricted T cell repertoire ex vivo with unexpected features, opening a new investigative path to study the human CD1 system.
authors.affiliation: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Anne G
authors.initials: AG
authors.lastname: Kasmar
authors.forename: Ildiko
authors.initials: I
authors.lastname: van Rhijn
authors.forename: Tan-Yun
authors.initials: TY
authors.lastname: Cheng
authors.forename: Marie
authors.initials: M
authors.lastname: Turner
authors.forename: Chetan
authors.initials: C
authors.lastname: Seshadri
authors.forename: Andre
authors.initials: A
authors.lastname: Schiefner
authors.forename: Ravi C
authors.initials: RC
authors.lastname: Kalathur
authors.forename: John W
authors.initials: JW
authors.lastname: Annand
authors.forename: Annemieke
authors.initials: A
authors.lastname: de Jong
authors.forename: John
authors.initials: J
authors.lastname: Shires
authors.forename: Luis
authors.initials: L
authors.lastname: Leon
authors.forename: Michael
authors.initials: M
authors.lastname: Brenner
authors.forename: Ian A
authors.initials: IA
authors.lastname: Wilson
authors.forename: John D
authors.initials: JD
authors.lastname: Altman
authors.forename: D Branch
authors.initials: DB
authors.lastname: Moody
mesh_terms: D000942:Antigens, Bacterial / Q000276:immunology* / Q000494:pharmacology; D018949:Antigens, CD1 / Q000235:genetics / Q000276:immunology*; D015704:CD4 Antigens / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D006017:Glycolipids / Q000276:immunology* / Q000494:pharmacology; D057809:HEK293 Cells; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D009161:Mycobacterium / Q000276:immunology*; D011485:Protein Binding / Q000187:drug effects / Q000276:immunology; D020836:Protein Structure, Quaternary; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D018949:Antigens, CD1; C419394:CD1b antigen; D015704:CD4 Antigens; D006017:Glycolipids; D016693:Receptors, Antigen, T-Cell, alpha-beta; C048938:glucose mycolate