Role of tripeptidyl peptidase II in MHC class I antigen processing - the end of controversies?
Peptide ligands presented by MHC class I molecules are generated in a cascade of proteolytic events starting with the proteasome in the cytosol and frequently terminating with trimming aminopeptidases in the endoplasmic reticulum. Several cytosolic proteases can carry out intermediate proteolytic steps between these start and endpoints. Among these, tripeptidyl peptidase II (TPP II), an exceptionally large homo-oligomeric protease, has been proposed to be involved in the generation of many or most MHC class I ligands by cleaving long precursor peptides. In this issue of the European Journal of Immunology, the effect of pharmacological or genetic TPP II inhibition on peptide loading of HLA-B27 and other HLA class I molecules is examined, and no evidence for a role of TPP II in this process is detected. Although further studies using more efficient inhibitors and focusing on HLA class I alleles such as HLA-A3 are warranted, these results, together with other recently published data, suggest that the role of TPP II in MHC class I processing may be much more limited than previously appreciated.
Endert
Peter van
Pv
Institut National de la Santé et de la Recherche Médicale, Unité 580, Paris, France. vanendert@necker.fr
D000626:Aminopeptidases / Q000378:metabolism; D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects / Q000276:immunology*; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D015796:HLA-B27 Antigen / Q000276:immunology / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D006801:Humans; D018448:Models, Immunological; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D012697:Serine Endopeptidases / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology
D015796:HLA-B27 Antigen; D015395:Histocompatibility Antigens Class I; D034741:RNA, Small Interfering; D015842:Serine Proteinase Inhibitors; D000626:Aminopeptidases; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; C048001:tripeptidyl-peptidase 2; D012697:Serine Endopeptidases; D046988:Proteasome Endopeptidase Complex