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Stoichiometric tapasin interactions in the catalysis of major histocompatibility complex class I molecule assembly
Author(s) -
Bangia Naveen,
Cresswell Peter
Publication year - 2005
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2005.02103.x
Subject(s) - transporter associated with antigen processing , mhc class i , major histocompatibility complex , calreticulin , microbiology and biotechnology , antigen processing , calnexin , chaperone (clinical) , chemistry , biology , endoplasmic reticulum , antigen , genetics , medicine , pathology
Summary 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.