DM and DO shape the repertoire of peptide-MHC-class-II complexes.
The presentation of antigenic peptides by MHC class II molecules is essential for activation of CD4+ T cells. The formation of most peptide-MHC-class-II complexes is influenced by the actions of two specialized accessory proteins--DM and DO--located in the endosomal/lysosomal system where peptide loading occurs. DM removes class-II-associated invariant-chain peptide (CLIP) from newly synthesized class II molecules, but by now it is clearly established that this is only a special case of the general peptide-editing function of DM. Recent data have begun to explain the molecular basis for the editing activity. The other accessory protein, DO, modulates DM activity in vitro, but the physiological importance of DO is unclear. New evidence from several laboratories has provided clues that may soon change this.
Karlsson
Lars
L
Johnson & Johnson Pharmaceutical Research and Development, 3210 Merryfield Row, San Diego, CA 92121, USA. lkarlsso@prdus.jnj.com
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D011992:Endosomes / Q000276:immunology; D006681:HLA-D Antigens / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D008247:Lysosomes / Q000276:immunology; D010455:Peptides / Q000276:immunology*
D000944:Antigens, Differentiation, B-Lymphocyte; D006681:HLA-D Antigens; C084245:HLA-DM antigens; C046148:HLA-DO antigens; D000949:Histocompatibility Antigens Class II; D010455:Peptides; C045084:invariant chain