Activation of human T cells by CD1 and self-lipids.
Over two decades ago, it was discovered that the human T-cell repertoire contains T cells that do not recognize peptide antigens in the context of MHC molecules but instead respond to lipid antigens presented by CD1 antigen-presenting molecules. The ability of T cells to 'see' lipid antigens bound to CD1 enables these lymphocytes to sense changes in the lipid composition of cells and tissues as a result of infections, inflammation, or malignancies. Although foreign lipid antigens have been shown to function as antigens for CD1-restricted T cells, many CD1-restricted T cells do not require foreign antigens for activation but instead can be activated by self-lipids presented by CD1. This review highlights recent developments in the field, including the identification of common mammalian lipids that function as autoantigens for αβ and γδ T cells, a novel mode of T-cell activation whereby CD1a itself rather than lipids serves as the autoantigen, and various mechanisms by which the activation of CD1-autoreactive T cells is regulated. As CD1 can induce T-cell effector functions in the absence of foreign antigens, multiple mechanisms are in place to regulate this self-reactivity, and stimulatory CD1-lipid complexes appear to be tightly controlled in space and time.
Department of Dermatology, Columbia University, New York, NY, USA.
Annemieke
A
de Jong
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D018949:Antigens, CD1 / Q000276:immunology* / Q000378:metabolism; D001324:Autoantigens / Q000276:immunology*; D006801:Humans; D008055:Lipids / Q000737:chemistry / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D018448:Models, Immunological; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D018949:Antigens, CD1; D001324:Autoantigens; D008055:Lipids; D011948:Receptors, Antigen, T-Cell
CD1 antigen-presenting molecules; T cells; lipid antigens