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Stoichiometric tapasin interactions in the catalysis of major histocompatibility complex class I molecule assembly
Authors:Bangia Naveen  Cresswell Peter
Affiliation:Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA. naveen.bangia@roswellpark.org
Abstract:The assembly of major histocompatibility complex (MHC) class I molecules with their peptide ligands in the endoplasmic reticulum (ER) requires the assistance of many proteins that form a multimolecular assemblage termed the 'peptide-loading complex'. Tapasin is the central stabilizer of this complex, which also includes the transporter associated with antigen processing (TAP), MHC class I molecules, the ER chaperone, calreticulin, and the thiol-oxidoreductase ERp57. In the present report, we investigated the requirements of these interactions for tapasin protein stability and MHC class I dissociation from the peptide-loading complex. We established that tapasin is stable in the absence of either TAP or MHC class I interaction. In the absence of TAP, tapasin interaction with MHC class I molecules is long-lived and results in the sequestration of existing tapasin molecules. In contrast, in TAP-sufficient cells, tapasin is re-utilized to interact with and facilitate the assembly of many MHC class I molecules sequentially. Furthermore, chemical cross-linking has been utilized to characterize the interactions within this complex. We demonstrate that tapasin and MHC class I molecules exist in a 1 : 1 complex without evidence of higher-order tapasin multimers. Together these studies shed light on the tapasin protein life cycle and how it functions in MHC class I assembly with peptide for presentation to CD8(+) T cells.
Keywords:MHC  protein stability  stoichiometry  TAP  tapasin
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引证文献(本文共被引2次):
[1]、David Stepensky,Naveen Bangia,Peter Cresswell *.Aggregate Formation by ERp57-Deficient MHC Class I Peptide-Loading Complexes[J].Traffic (Copenhagen, Denmark),2007,8(11):1530-1542.
[2]、Eric D. Landis, Yniv Palti, Jenefer Dekoning, Robert Drew, Ruth B. Phillips and John D. Hansen.Identification and regulatory analysis of rainbow trout tapasin and tapasin-related genes[J].Immunogenetics,2006,58(1):56-69.
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