Selection of the MHC class II-associated peptide repertoire by HLA-DM.
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.
Arndt
S O
SO
Department of Molecular Immunology, German Cancer Research Center, Heildelberg, Germany.
Vogt
A B
AB
Hämmerling
G J
GJ
Kropshofer
H
H
D000818:Animals; D017951:Antigen Presentation; D006681:HLA-D Antigens / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D008024:Ligands; D010449:Peptide Mapping
C416189:H2-M antigens; D006681:HLA-D Antigens; C084245:HLA-DM antigens; D000949:Histocompatibility Antigens Class II; D008024:Ligands