title: The human CD1-restricted T cell repertoire is limited to cross-reactive antigens: implications for host responses against immunologically related pathogens.
abstract: The repertoires of CD1- and MHC-restricted T cells are complementary, permitting the immune recognition of both lipid and peptide Ags, respectively. To compare the breadth of the CD1-restricted and MHC-restricted T cell repertoires, we evaluated T cell responses against lipid and peptide Ags of mycobacteria in leprosy, comparing tuberculoid patients, who are able to restrict the pathogen, and lepromatous patients, who have disseminated infection. The striking finding was that in lepromatous leprosy, T cells did not efficiently recognize lipid Ags from the leprosy pathogen, Mycobacterium leprae, or the related species, Mycobacterium tuberculosis, yet were able to efficiently recognize peptide Ags from M. tuberculosis, but not M. leprae. To identify a mechanism for T cell unresponsiveness against mycobacterial lipid Ags in lepromatous patients, we used T cell clones to probe the species specificity of the Ags recognized. We found that the majority of M. leprae-reactive CD1-restricted T cell clones (92%) were cross-reactive for multiple mycobacterial species, whereas the majority of M. leprae-reactive MHC-restricted T cells were species specific (66%), with a limited number of T cell clones cross-reactive (34%) with M. tuberculosis. In comparison with the MHC class II-restricted T cell repertoire, the CD1-restricted T cell repertoire is limited to recognition of cross-reactive Ags, imparting a distinct role in the host response to immunologically related pathogens.
authors.affiliation: Division of Dermatology, David Geffen School of Medicine at University of California-Los Angeles, Los Angeles, CA 90095, USA. pseiling@mednet.ucla.edu
authors.forename: Peter A
authors.initials: PA
authors.lastname: Sieling
authors.forename: Jordi B
authors.initials: JB
authors.lastname: Torrelles
authors.forename: Steffen
authors.initials: S
authors.lastname: Stenger
authors.forename: Woosin
authors.initials: W
authors.lastname: Chung
authors.forename: Anne E
authors.initials: AE
authors.lastname: Burdick
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Rea
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Brennan
authors.forename: John T
authors.initials: JT
authors.lastname: Belisle
authors.forename: Steven A
authors.initials: SA
authors.lastname: Porcelli
authors.forename: Robert L
authors.initials: RL
authors.lastname: Modlin
mesh_terms: D000328:Adult; D000368:Aged; D017951:Antigen Presentation; D018949:Antigens, CD1 / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000378:metabolism; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D015440:Leprosy, Lepromatous / Q000276:immunology / Q000382:microbiology; D008055:Lipids / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D009166:Mycobacterium leprae / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D014376:Tuberculosis / Q000276:immunology / Q000382:microbiology
chemical_list: D018949:Antigens, CD1; D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; D008055:Lipids; D011948:Receptors, Antigen, T-Cell