title: Major T cell response to a mycolyl glycolipid is mediated by CD1c molecules in rhesus macaques.
abstract: Human CD1b molecules contain a maze of hydrophobic pockets and a tunnel capable of accommodating the unusually long, branched acyl chain of mycolic acids, an essential fatty acid component of the cell wall of mycobacteria. It has been accepted that CD1b-bound mycolic acids constitute a scaffold for mycolate-containing (glyco)lipids stimulating CD1b-restricted T cells. Remarkable homology in amino acid sequence is observed between human and monkey CD1b molecules, and indeed, monkey CD1b molecules are able to bind glucose monomycolate (GMM), a glucosylated species of mycolic acids, and present it to specific human T cells in vitro. Nevertheless, we found, unexpectedly, that Mycobacterium bovis bacillus Calmette-Guerin (BCG)-vaccinated monkeys exhibited GMM-specific T cell responses that were restricted by CD1c rather than CD1b molecules. GMM-specific, CD1c-restricted T cells were detected in the circulation of all 4 rhesus macaque monkeys tested after but not before vaccination with BCG. The circulating GMM-specific T cells were detected broadly in both CD4(+) and CD8(+) cell populations, and upon antigenic stimulation, a majority of the GMM-specific T cells produced both gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α), two major host protective cytokines functioning against infection with mycobacteria. Furthermore, the GMM-specific T cells were able to extravasate and approach the site of infection where CD1c(+) cells accumulated. These observations indicate a previously inconceivable role for primate CD1c molecules in eliciting T cell responses to mycolate-containing antigens.
authors.affiliation: Laboratory of Cell Regulation, Institute for Virus Research, Kyoto University, Kyoto, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Morita
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hattori
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakamura
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Igarashi
authors.forename: Hideyoshi
authors.initials: H
authors.lastname: Harashima
authors.forename: Masahiko
authors.initials: M
authors.lastname: Sugita
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology / Q000378:metabolism; D018949:Antigens, CD1 / Q000276:immunology* / Q000378:metabolism; D001500:BCG Vaccine / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D006017:Glycolipids / Q000276:immunology* / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D008253:Macaca mulatta / Q000276:immunology* / Q000378:metabolism; D009161:Mycobacterium / Q000276:immunology* / Q000378:metabolism; D009164:Mycobacterium Infections / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D009163:Mycobacterium bovis / Q000276:immunology / Q000378:metabolism; D009171:Mycolic Acids / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
chemical_list: D000942:Antigens, Bacterial; D018949:Antigens, CD1; D001500:BCG Vaccine; D006017:Glycolipids; D009171:Mycolic Acids; D014409:Tumor Necrosis Factor-alpha; C048938:glucose mycolate; D007371:Interferon-gamma