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Productive association between MHC class I and tapasin requires the tapasin transmembrane/cytosolic region and the tapasin C-terminal Ig-like domain.


ABSTRACT: The current model of antigen assembly with major histocompatibility complex (MHC) class I molecules posits that interactions between the tapasin N-terminal immunoglobulin (Ig)-like domain and the MHC class I peptide-binding groove permit tapasin to regulate antigen selection. Much less is known regarding interactions that might involve the tapasin C-terminal Ig-like domain. Additionally, the tapasin transmembrane/cytoplasmic region enables tapasin to bridge the MHC class I molecule to the transporter associated with antigen processing (TAP). In this investigation, we made use of two tapasin mutants to determine the relative contribution of the tapasin C-terminal Ig-like domain and the tapasin transmembrane/cytoplasmic region to the assembly of MHC class I molecules. Deletion of a loop within the tapasin C-terminal Ig-like domain (?334-342) prevented tapasin association with the MHC class I molecule K(d). Although tapasin ?334-342 did not increase the efficiency of K(d) folding, K(d) surface expression was enhanced on cells expressing this mutant relative to tapasin-deficient cells. In contrast to tapasin ?334-342, a soluble tapasin mutant lacking the transmembrane/cytoplasmic region retained the ability to bind to K(d) molecules, but did not facilitate K(d) surface expression. Furthermore, when soluble tapasin and tapasin ?334-342 were co-expressed, soluble tapasin had a dominant negative effect on the folding and surface expression of not only K(d), but also D(b) and K(b). In addition, our molecular modeling of the MHC class I-tapasin interface revealed novel potential interactions involving tapasin residues 334-342. Together, these findings demonstrate that the tapasin C-terminal and transmembrane/cytoplasmic regions are critical to tapasin's capacity to associate effectively with the MHC class I molecule.

SUBMITTER: Simone LC 

PROVIDER: S-EPMC3249531 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature

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Productive association between MHC class I and tapasin requires the tapasin transmembrane/cytosolic region and the tapasin C-terminal Ig-like domain.

Simone Laura C LC   Georgesen Corey J CJ   Simone Peter D PD   Wang Xiaojian X   Solheim Joyce C JC  

Molecular immunology 20111212 4


The current model of antigen assembly with major histocompatibility complex (MHC) class I molecules posits that interactions between the tapasin N-terminal immunoglobulin (Ig)-like domain and the MHC class I peptide-binding groove permit tapasin to regulate antigen selection. Much less is known regarding interactions that might involve the tapasin C-terminal Ig-like domain. Additionally, the tapasin transmembrane/cytoplasmic region enables tapasin to bridge the MHC class I molecule to the transp  ...[more]

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