title: Running the gauntlet: from peptide generation to antigen presentation by MHC class I.
abstract: Major histocompatibility complex (MHC) class I molecules provide the molecular basis for the comprehensive surveillance of an organism by the cytotoxic arm of the adaptive immune system. To exert this function correctly, class I molecules must be loaded with peptide ligands of appropriate length, sequence and affinity that provide a rapidly updated and sufficiently comprehensive picture of the state of the cell. This is accomplished by a sophisticated cellular machinery using a blend of cellular house-keeping proteins and dedicated transporters, chaperones and peptidases. The last 10 years have seen substantial progress in our comprehension of this machinery. It seems now clear that a large proportion of MHC class I ligands are derived from short-lived products of the ribosomal apparatus, many of which correspond to defective proteins. Despite much effort to identify alternative proteolytic pathways, cytosolic production of epitopes still appears to depend almost entirely on the proteasome, while cytosolic aminopeptidases act mainly to limit antigen presentation. In contrast, clear evidence for a critical role of trimming peptidases residing in the endoplasmic reticulum has emerged. These enzymes play a role in responses against pathogens and are associated with autoimmune diseases, most notably ankylosing spondylitis. Much has also been learned about the intricate chaperone interactions in peptide-loading complexes, especially with respect to the structural role of tapasin-ERp57 conjugates and to the editing function of tapasin. In contrast, cross-presentation of exogenous antigens by MHC class I molecules still remains somewhat poorly understood and is likely to attract much research effort for years to come.
authors: Institut National de la Santé et de la Recherche Médicale, Unité 1013, Paris, France.
authors: P M
authors: PM
authors: Saunders
authors: P
authors: P
authors: van Endert
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism*
chemical_list: D015395:Histocompatibility Antigens Class I; D010446:Peptide Fragments