title: A conserved human T cell population targets mycobacterial antigens presented by CD1b.
abstract: Human T cell antigen receptors (TCRs) pair in millions of combinations to create complex and unique T cell repertoires for each person. Through the use of tetramers to analyze TCRs reactive to the antigen-presenting molecule CD1b, we detected T cells with highly stereotyped TCR α-chains present among genetically unrelated patients with tuberculosis. The germline-encoded, mycolyl lipid-reactive (GEM) TCRs had an α-chain bearing the variable (V) region TRAV1-2 rearranged to the joining (J) region TRAJ9 with few nontemplated (N)-region additions. Analysis of TCRs by high-throughput sequencing, binding and crystallography showed linkage of TCRα sequence motifs to high-affinity recognition of antigen. Thus, the CD1-reactive TCR repertoire is composed of at least two compartments: high-affinity GEM TCRs, and more-diverse TCRs with low affinity for CD1b-lipid complexes. We found high interdonor conservation of TCRs that probably resulted from selection by a nonpolymorphic antigen-presenting molecule and an immunodominant antigen.
authors.affiliation: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. i.vanrhijn@uu.nl
authors.forename: Ildiko
authors.initials: I
authors.lastname: Van Rhijn
authors.forename: Anne
authors.initials: A
authors.lastname: Kasmar
authors.forename: Annemieke
authors.initials: A
authors.lastname: de Jong
authors.forename: Stephanie
authors.initials: S
authors.lastname: Gras
authors.forename: Mugdha
authors.initials: M
authors.lastname: Bhati
authors.forename: Marieke E
authors.initials: ME
authors.lastname: Doorenspleet
authors.forename: Niek
authors.initials: N
authors.lastname: de Vries
authors.forename: Dale I
authors.initials: DI
authors.lastname: Godfrey
authors.forename: John D
authors.initials: JD
authors.lastname: Altman
authors.forename: Wilco
authors.initials: W
authors.lastname: de Jager
authors.forename: Jamie
authors.initials: J
authors.lastname: Rossjohn
authors.forename: D Branch
authors.initials: DB
authors.lastname: Moody
mesh_terms: D000595:Amino Acid Sequence; D018949:Antigens, CD1 / Q000276:immunology*; D001483:Base Sequence; D002999:Clone Cells; D018360:Crystallography, X-Ray; D005434:Flow Cytometry; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009161:Mycobacterium / Q000276:immunology*; D009164:Mycobacterium Infections / Q000276:immunology* / Q000382:microbiology; D012313:RNA / Q000737:chemistry / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
chemical_list: D018949:Antigens, CD1; D016693:Receptors, Antigen, T-Cell, alpha-beta; D012313:RNA