Mechanisms of lipid antigen presentation by CD1.
CD1 is a family of cell surface glycoproteins that are related in structure and evolutionary origin to the major histocompatibility complex (MHC)-encoded antigen-presenting molecules. In contrast to MHC-encoded antigen-presenting molecules, CD1 binds and presents lipid and glycolipid antigens for specific recognition by T cell antigen receptors. Recent work shows that several CD1 family members colocalize with MHC class II proteins within the endocytic system of antigen-presenting cells. Detailed studies of the intracellular trafficking of CD1 proteins reveal new mechanisms controlling delivery of antigen-presenting molecules to particular compartments within cells. The combination of overlapping yet distinct trafficking routes for the various CD1 family members, combined with emerging information on the heterogeneity of CD1-presented lipid antigens, suggest a model whereby different members of the CD1 family could present antigens that occur in various cellular compartments. Furthermore, the CD1 family as a group may present antigens from pathogens that are not normally accessible to or efficiently surveyed by the MHC Class I or II systems. The discovery of this third pathway for antigen presentation, together with the appreciation of a previously unrecognized universe of nonpeptide lipid antigens for T cell responses, are likely to have broad implications for our understanding of the cell-mediated immune response and its role in health and disease.
Jackman
R M
RM
Lymphocyte Biology Section, Brigham and Women's Hospital, Boston, MA 02115, USA.
Moody
D B
DB
Porcelli
S A
SA
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D018949:Antigens, CD1 / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D001692:Biological Transport; D006649:Histocompatibility Antigens / Q000276:immunology / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry / Q000276:immunology*; D011487:Protein Conformation; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism