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http://purl.uniprot.org/citations/8805302http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/8805302http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/8805302http://www.w3.org/2000/01/rdf-schema#comment"

Background

Glycoproteins encoded by the major histocompatibility complex class I region (MHC class I) present peptide antigens to cytotoxic T cells (CTLs). Peptides are delivered to the site of MHC class I assembly by the transporter associated with antigen processing (TAP), and cell lines that lack this transporter are unable to present endogenous antigens to CTLs. Although it has been shown that a fraction of newly synthesized class I molecules are in physical association with TAP, it is not known whether this interaction is functionally relevant, or where on the class I molecule the TAP binding site might be.

Results

C1R cells transfected with a mutant HLA-A2.1 heavy chain (HC), where threonine at position 134 in the alpha 2 domain is changed to lysine (T134K), are unable to present endogenous antigens to CTLs. We have studied the biochemistry of this mutant in C1R cells, and found that a large pool of unstable empty class I HC-beta 2m (beta-2 microglobulin) heterodimers exist that are rapidly transported to the cell surface. The T134K mutant seemed to bind peptide antigens and assemble with beta 2m as efficiently as wild-type HLA-A2.1. However, we show here that the inefficiency with which T134K presents intracellular antigen is associated with its inability to interact with the TAP heterodimer.

Conclusions

These experiments establish that the class I-TAP interaction is obligatory for the presentation of peptide epitopes delivered to the endoplasmic reticulum (ER) by TAP. Wild-type HLA-A2.1 molecules in TAP-deficient cells are retained in the ER, whereas T134K is rapidly released to the cell surface, but is unstable, suggesting a role for the TAP complex as an intracellular checkpoint that only affects the release of class I molecules with stably bound peptide ligands."xsd:string
http://purl.uniprot.org/citations/8805302http://purl.org/dc/terms/identifier"doi:10.1016/s0960-9822(02)00611-5"xsd:string
http://purl.uniprot.org/citations/8805302http://purl.org/dc/terms/identifier"doi:10.1016/s0960-9822(02)00611-5"xsd:string
http://purl.uniprot.org/citations/8805302http://purl.uniprot.org/core/author"Elliott T."xsd:string
http://purl.uniprot.org/citations/8805302http://purl.uniprot.org/core/author"Elliott T."xsd:string
http://purl.uniprot.org/citations/8805302http://purl.uniprot.org/core/author"Neefjes J."xsd:string
http://purl.uniprot.org/citations/8805302http://purl.uniprot.org/core/author"Neefjes J."xsd:string
http://purl.uniprot.org/citations/8805302http://purl.uniprot.org/core/author"Neisig A."xsd:string
http://purl.uniprot.org/citations/8805302http://purl.uniprot.org/core/author"Neisig A."xsd:string
http://purl.uniprot.org/citations/8805302http://purl.uniprot.org/core/author"Lewis J.W."xsd:string
http://purl.uniprot.org/citations/8805302http://purl.uniprot.org/core/author"Lewis J.W."xsd:string
http://purl.uniprot.org/citations/8805302http://purl.uniprot.org/core/date"1996"xsd:gYear
http://purl.uniprot.org/citations/8805302http://purl.uniprot.org/core/date"1996"xsd:gYear
http://purl.uniprot.org/citations/8805302http://purl.uniprot.org/core/name"Curr. Biol."xsd:string
http://purl.uniprot.org/citations/8805302http://purl.uniprot.org/core/name"Curr. Biol."xsd:string
http://purl.uniprot.org/citations/8805302http://purl.uniprot.org/core/pages"873-883"xsd:string
http://purl.uniprot.org/citations/8805302http://purl.uniprot.org/core/pages"873-883"xsd:string
http://purl.uniprot.org/citations/8805302http://purl.uniprot.org/core/title"Point mutations in the alpha 2 domain of HLA-A2.1 define a functionally relevant interaction with TAP."xsd:string
http://purl.uniprot.org/citations/8805302http://purl.uniprot.org/core/title"Point mutations in the alpha 2 domain of HLA-A2.1 define a functionally relevant interaction with TAP."xsd:string
http://purl.uniprot.org/citations/8805302http://purl.uniprot.org/core/volume"6"xsd:string
http://purl.uniprot.org/citations/8805302http://purl.uniprot.org/core/volume"6"xsd:string
http://purl.uniprot.org/citations/8805302http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/8805302
http://purl.uniprot.org/citations/8805302http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/8805302
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