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 H molecules. Unlike the MHC molecules, which bind short peptides in their antigen-binding groove for presentation to either CD4⁺ or CD8⁺ T cells bearing αβ 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 αβ and γδ T cells and CD8⁺ αβ 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-γ, 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.