CD1--a new paradigm for antigen presentation and T cell activation.
Despite identification of the CD1 family of molecules in the late 1970s, the function of CD1 was undetermined for more than a decade. Recent evidence has established that CD1 molecules comprise a novel lineage of antigen-presenting molecules, distinct from major histocompatibility complex (MHC) class I and class II molecules. Unlike the MHC molecules, which bind short peptides in their antigen-binding groove for presentation to either CD4+ or CD8+ T cells bearing alpha beta T cell receptors, the CD1 molecules appear to accommodate lipid and glycolipid antigens in their hydrophobic cavity for presentation to a wide variety of T cells, including double-negative alpha beta and gamma delta T cells and CD8+ alpha beta T cells. By using a unique cytoplasmic signal, some CD1 molecules traffic to endosomal compartments for sampling mycobacteria-derived lipid antigens, and subsequently lipid antigen-loaded CD1 molecules are expressed on the cell surface to activate specific T cells. These CD1-restricted T cells kill mycobacteria-infected cells and secrete interferon-gamma, indicating a potential role of CD1-mediated T cell responses in clearing mycobacterial infection. The identification of an MHC-independent antigen presentation pathway for nonpeptide antigens provides new insights into immunoregulation and host defense.
Sugita
M
M
Lymphocyte Biology Section, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Moody
D B
DB
Jackman
R M
RM
Grant
E P
EP
Rosat
J P
JP
Behar
S M
SM
Peters
P J
PJ
Porcelli
S A
SA
Brenner
M B
MB
D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology; D018949:Antigens, CD1 / Q000502:physiology*; D004705:Endocytosis; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D008055:Lipids / Q000276:immunology; D008213:Lymphocyte Activation; D009161:Mycobacterium / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000942:Antigens, Bacterial; D018949:Antigens, CD1; D000949:Histocompatibility Antigens Class II; D008055:Lipids