title: TCR bias and affinity define two compartments of the CD1b-glycolipid-specific T Cell repertoire.
abstract: Current views emphasize TCR diversity as a key feature that differentiates the group 1 (CD1a, CD1b, CD1c) and group 2 (CD1d) CD1 systems. Whereas TCR sequence motifs define CD1d-reactive NKT cells, the available data do not allow a TCR-based organization of the group 1 CD1 repertoire. The observed TCR diversity might result from donor-to-donor differences in TCR repertoire, as seen for MHC-restricted T cells. Alternatively, diversity might result from differing CD1 isoforms, Ags, and methods used to identify TCRs. Using CD1b tetramers to isolate clones recognizing the same glycolipid, we identified a previously unknown pattern of V gene usage (TRAV17, TRBV4-1) among unrelated human subjects. These TCRs are distinct from those present on NKT cells and germline-encoded mycolyl lipid-reactive T cells. Instead, they resemble the TCR of LDN5, one of the first known CD1b-reactive clones that was previously thought to illustrate the diversity of the TCR repertoire. Interdonor TCR conservation was observed in vitro and ex vivo, identifying LDN5-like T cells as a distinct T cell type. These data support TCR-based organization of the CD1b repertoire, which consists of at least two compartments that differ in TCR sequence motifs, affinity, and coreceptor expression.
authors.affiliation: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115;
authors.forename: Ildiko
authors.initials: I
authors.lastname: Van Rhijn
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Gherardin
authors.forename: Anne
authors.initials: A
authors.lastname: Kasmar
authors.forename: Wilco
authors.initials: W
authors.lastname: de Jager
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Pellicci
authors.forename: Lyudmila
authors.initials: L
authors.lastname: Kostenko
authors.forename: Li Lynn
authors.initials: LL
authors.lastname: Tan
authors.forename: Mugdha
authors.initials: M
authors.lastname: Bhati
authors.forename: Stephanie
authors.initials: S
authors.lastname: Gras
authors.forename: Dale I
authors.initials: DI
authors.lastname: Godfrey
authors.forename: Jamie
authors.initials: J
authors.lastname: Rossjohn
authors.forename: D Branch
authors.initials: DB
authors.lastname: Moody
mesh_terms: D020816:Amino Acid Motifs / Q000276:immunology*; D018949:Antigens, CD1 / Q000276:immunology; D001483:Base Sequence; D017124:Conserved Sequence / Q000276:immunology; D005434:Flow Cytometry; D006017:Glycolipids / Q000276:immunology; D006801:Humans; D008969:Molecular Sequence Data; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry* / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000737:chemistry* / Q000276:immunology
chemical_list: D018949:Antigens, CD1; C419394:CD1b antigen; D006017:Glycolipids; D011948:Receptors, Antigen, T-Cell