title: CD1 and mycobacterial lipids activate human T cells.
abstract: For decades, proteins were thought to be the sole or at least the dominant source of antigens for T cells. Studies in the 1990s demonstrated that CD1 proteins and mycobacterial lipids form specific targets of human αβ T cells. The molecular basis by which T-cell receptors (TCRs) recognize CD1-lipid complexes is now well understood. Many types of mycobacterial lipids function as antigens in the CD1 system, and new studies done with CD1 tetramers identify T-cell populations in the blood of tuberculosis patients. In human populations, a fundamental difference between the CD1 and major histocompatibility complex systems is that all humans express nearly identical CD1 proteins. Correspondingly, human CD1 responsive T cells show evidence of conserved TCRs. In addition to natural killer T cells and mucosal-associated invariant T (MAIT cells), conserved TCRs define other subsets of human T cells, including germline-encoded mycolyl-reactive (GEM) T cells. The simple immunogenetics of the CD1 system and new investigative tools to measure T-cell responses in humans now creates a situation in which known lipid antigens can be developed as immunodiagnostic and immunotherapeutic reagents for tuberculosis disease.
authors.affiliation: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
authors.forename: Ildiko
authors.initials: I
authors.lastname: Van Rhijn
authors.forename: D Branch
authors.initials: DB
authors.lastname: Moody
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000942:Antigens, Bacterial / Q000276:immunology* / Q000378:metabolism; D018949:Antigens, CD1 / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001692:Biological Transport; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D011992:Endosomes / Q000378:metabolism; D000939:Epitopes / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D050356:Lipid Metabolism; D008055:Lipids / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D009928:Organ Specificity / Q000235:genetics; D010743:Phospholipids / Q000276:immunology / Q000378:metabolism; D055503:Protein Multimerization; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D014376:Tuberculosis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology
chemical_list: D000942:Antigens, Bacterial; D018949:Antigens, CD1; D000939:Epitopes; D008055:Lipids; D010743:Phospholipids
keywords: CD1; Mycobacterium tuberculosis; T cells; T-cell receptor; mycolyl lipids