Selection of the MHC class II-associated peptide repertoire by HLA-DM

• Published in: Immunologic research Vol. 16; no. 3; pp. 261 - 272
• Main Authors: Arndt, S O, Vogt, A B, Hämmerling, G J, Kropshofer, H
• Format: Journal Article
• Language: English
• Published: United States Springer Nature B.V 01.08.1997
• Subjects: Animals; Antigen Presentation; Antigens; Cell lines; Grooves; Helper cells; Histocompatibility antigen HLA; Histocompatibility Antigens Class II - immunology; HLA-D Antigens - immunology; Humans; Immunology; Inactivation; Ligands; Major histocompatibility complex; Peptide Mapping; Peptides; Proteins; Stability; T cell receptors
• ISSN: 0257-277X; 1559-0755
• DOI: 10.1007/BF02786394

During the past five years considerable progress has been made in the field of major histocompatibility complex (MHC) class II-restricted antigen presentation. Several observations made in mutant cell lines with a presentation defect led to the identification of a novel protein, the nonclassic MHC class II molecule human leukocyte antigen (HLA)-DM. Cell biological and biochemical characterization of HLA-DM provided deeper insight into the molecular mechanism underlying the loading process: HLA-DM accumulates in acidic compartments where it binds to classic class II molecules as long as no high-stability ligand occupies the peptide-binding groove. Thus, HLA-DM prevents empty alpha beta dimers from functional inactivation in a chaperone-like fashion. At the same time HLA-DM acts as an editor by removing low-stability ligands, thereby skewing the class II peptide repertoire presentable to T-helper cells.