CD1 - A NEW PARADIGM FOR ANTIGEN PRESENTATION AND T-CELL ACTIVATION

Despite identification of the CD1 family of molecules in the late 1970 s, 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 histocompatibilit y complex (MHC) class I and class II molecules. Unlike the MHC molecul es, which bind short peptides in their antigen-binding groove for pres entation to either CD4(+) or CD8(+) T cells bearing alpha beta T cell receptors, the CD1 molecules appear to accommodate lipid and glycolipi d antigens in their hydrophobic cavity for presentation to a wide vari ety of T cells, including double-negative alpha beta and gamma delta T cells and CD8(+) alpha beta T cells. By using a unique cytoplasmic si gnal, some CD1 molecules traffic to endosomal compartments for samplin g mycobacteria-derived lipid antigens, and subsequently lipid antigen- loaded CD1 molecules are expressed on the cell surface to activate spe cific T cells. These CD1-restricted T cells kill mycobacteria-infected cells and secrete interferon-gamma, indicating a potential role of CD 1-mediated T cell responses in clearing mycobacterial infection. The i dentification of an MHC-independent antigen presentation pathway for n onpeptide antigens provides new insights into immunoregulation and hos t defense. (C) 1998 Academic Press.