The outermost N-terminal region of tapasin facilitates folding of major histocompatibility complex class I

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Bibtex

@article{e5363cdd760a4d92bd19e90ecd7a63fd,
title = "The outermost N-terminal region of tapasin facilitates folding of major histocompatibility complex class I",
abstract = "Tapasin (Tpn) is an ER chaperone that is uniquely dedicated to MHC-I biosynthesis. It binds MHC-I molecules, integrates them into peptide-loading complexes, and exerts quality control of the bound peptides; only when an {"}optimal peptide{"} is bound will the MHC-I be released and exported to the cell surface for presentation to T cells. The exact mechanisms of Tpn quality control and the criteria for being an optimal peptide are still unknown. Here, we have generated a recombinant fragment of human Tpn, Tpn(1-87) (representing the 87 N-terminal and ER-luminal amino acids of the mature Tpn protein). Using a biochemical peptide-MHC-I-binding assay, recombinant Tpn(1-87) was found to specifically facilitate peptide-dependent folding of HLA-A*0201. Furthermore, we used Tpn(1-87) to generate a monoclonal antibody, alpha Tpn(1-87/80), specific for natural human Tpn and capable of cellular staining of ER localized Tpn. Using overlapping peptides, the epitope of alpha Tpn(1-87)/80 was located to Tpn(40-44), which maps to a surface-exposed loop on the Tpn structure. Together, these results demonstrate that the N-terminal region of Tpn can be recombinantly expressed and adopt a structure, which at least partially resembles that of WT Tpn, and that this region of Tpn features chaperone activity facilitating peptide binding of MHC-I.",
keywords = "Antibodies, Antigen processing, MHC-I",
author = "Gustav Roder and {Geironson Ulfsson}, Linda and Anna Darabi and Mikkel Harndahl and Claus Schafer-Nielsen and Karsten Skjodt and Soren Buus and Paulsson, {Kajsa M}",
year = "2009",
doi = "10.1002/eji.200939364",
language = "English",
volume = "39",
pages = "2682--2694",
journal = "European Journal of Immunology",
issn = "1521-4141",
publisher = "John Wiley and Sons Inc.",
number = "10",

}