HLA-DM, HLA-DO and tapasin: functional similarities and differences.
In both the MHC class II and class I pathways of antigen presentation, accessory molecules influence formation of MHC-peptide complexes. In the MHC class II pathway, DM functions in the loading and editing of peptides; recent work demonstrated that it is acting not only in late endosomal compartments but also in recycling compartments and on the surface of B cells and immature dendritic cells. DM activity is modulated by another accessory molecule, DO, but this modulation is mainly operative in B cells, where it may lead to preferential activation of B cells producing high-affinity antibodies. In the MHC class I pathway of antigen presentation, recent in vivo experiments with knockout mice confirmed the role of tapasin in antigen presentation and indicate that it acts as a peptide editor and as a chaperone for TAP and the MHC class I heavy chain. In the class I loading complex, calreticulin and the thiol-dependent oxidoreductase ER60/ERp57 appear to support the function of tapasin in an as-yet-unknown fashion. The picture emerges that DM and tapasin have analogous functions in shaping the peptide repertoire presented by the respective MHC class II and class I molecules.
Brocke
Pascale
P
DKFZ Deutsches Krebsforschungszentrum, German Cancer Research Center, Molecular Immunology, Im Neuenheimer Feld 280, D-69120, Heidelberg, Germany.
Garbi
Natalio
N
Momburg
Frank
F
Hämmerling
Günter J
GJ
D000818:Animals; D017951:Antigen Presentation; D017920:Antiporters / Q000276:immunology*; D006681:HLA-D Antigens / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology*; D026901:Membrane Transport Proteins; D051379:Mice; D018345:Mice, Knockout
D017920:Antiporters; D006681:HLA-D Antigens; C084245:HLA-DM antigens; C046148:HLA-DO antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007136:Immunoglobulins; D026901:Membrane Transport Proteins; C107762:tapasin