The transporter associated with antigen processing TAP: structure and function

Lankat–Buttgereit, Brigitte; Tampé, Robert

doi:10.1016/s0014-5793(99)01676-2

Cited by 56 publications

(39 citation statements)

References 51 publications

(46 reference statements)

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“…Similar results have been reported by others (18,31,32). The primary interaction of TCR is with residues 5-8 of a class I MHC binding nonapeptide (36).…”

Section: Discussionsupporting

confidence: 89%

“…Many studies have suggested that the peptide selectivity exhibited by TAP binding may contribute to epitope selection (18,(31)(32)(33). To assess quantitatively the impact of this preselection for alleles that are strongly or weakly TAP dependent, two ROC analyses were performed.…”

Section: Tap Preselection Of Mhc Bindersmentioning

confidence: 99%

“…Unsurprisingly, TAP preselection was more efficient for fully TAP-dependent alleles than for partially TAP-dependent alleles. Positions 1, 2, 3, and 9 were the most significant for binding to TAP (18,31,32). To test their contributions to MHC binding prediction, models considering the amino acid contributions at these positions were developed and applied to A*0201 binder/nonbinder test set (Fig.…”

Section: Figure 2 Roc Curves Of Tap Hla-a*0201 (A)mentioning

confidence: 99%

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Transporter Associated with Antigen Processing Preselection of Peptides Binding to the MHC: A Bioinformatic Evaluation

Doytchinova

Hemsley

Flower

2004

The Journal of Immunology

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TAP is responsible for the transit of peptides from the cytosol to the lumen of the endoplasmic reticulum. In an immunological context, this event is followed by the binding of peptides to MHC molecules before export to the cell surface and recognition by T cells. Because TAP transport precedes MHC binding, TAP preferences may make a significant contribution to epitope selection. To assess the impact of this preselection, we have developed a scoring function for TAP affinity prediction using the additive method, have used it to analyze and extend the TAP binding motif, and have evaluated how well this model acts as a preselection step in predicting MHC binding peptides. To distinguish between MHC alleles that are exclusively dependent on TAP and those exhibiting only a partial dependence on TAP, two sets of MHC binding peptides were examined: HLA-A*0201 was selected as a representative of partially TAP-dependent HLA alleles, and HLA-A*0301 represented fully TAP-dependent HLA alleles. TAP preselection has a greater impact on TAP-dependent alleles than on TAP-independent alleles. The reduction in the number of nonbinders varied from 10% (TAP-independent) to 33% (TAP-dependent), suggesting that TAP preselection is an important component in the successful in silico prediction of T cell epitopes.

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“…Similar results have been reported by others (18,31,32). The primary interaction of TCR is with residues 5-8 of a class I MHC binding nonapeptide (36).…”

Section: Discussionsupporting

confidence: 89%

Section: Tap Preselection Of Mhc Bindersmentioning

confidence: 99%

Section: Figure 2 Roc Curves Of Tap Hla-a*0201 (A)mentioning

confidence: 99%

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Transporter Associated with Antigen Processing Preselection of Peptides Binding to the MHC: A Bioinformatic Evaluation

Doytchinova

Hemsley

Flower

2004

The Journal of Immunology

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“…Peptides presented by MHC class I molecules are generated predominantly in the cytoplasm by the proteasome (1). Transport of antigenic peptides from the cytoplasm into the endoplasmic reticulum (ER) 3 by TAP for loading onto MHC class I molecules is a key step in the Ag presentation pathway (1). TAP is a member of the ATP-binding cassette (ABC) transporter family whose members translocate different types of substrates across cellular membranes using energy from ATP hydrolysis (2).…”

Section: Functional Role Of C-terminal Sequence Elements In Thementioning

confidence: 99%

“…Each of the two subunits of the heterodimeric TAP, TAP1 and TAP2, has an N-terminal TMD and a C-terminal NBD. The paired TMDs of TAP form the peptide-binding site and the pore through which peptide substrates are translocated, whereas the NBDs provide the energy required for peptide transport by ATP hydrolysis (3).…”

Section: Functional Role Of C-terminal Sequence Elements In Thementioning

confidence: 99%

Functional Role of C-Terminal Sequence Elements in the Transporter Associated with Antigen Processing

Ehses

Leonhardt

Hansen

et al. 2005

The Journal of Immunology

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TAP delivers antigenic peptides into the endoplasmic reticulum (ER) that are subsequently bound by MHC class I molecules. TAP consists of two subunits (TAP1 and TAP2), each with a transmembrane (TMD) and a nucleotide-binding (NBD) domain. The two TAP-NBDs have distinct biochemical properties and control different steps during the peptide translocation process. We noted previously that the nonhomologous C-terminal tails of rat TAP1 and TAP2 determine the distinct functions of TAP-NBD1 and -NBD2. To identify the sequence elements responsible for the asymmetrical NBD function, we constructed chimeric rat TAP variants in which we systematically exchanged sequence regions of different length between the two TAP-NBDs. Our fine-mapping studies demonstrate that a nonhomologous region containing the α6/β10-loop in conjunction with the downstream switch region is directly responsible for the functional separation of the TAP-NBDs. The α6/β10-loop determines the nonsynonymous nucleotide binding of NBD1 and NBD2, whereas the switch region seems to play a critical role in regulating the functional cross-talk between the structural domains of TAP. Based on our findings, we postulate that these two sequence elements build a minimal functional unit that controls the asymmetry of the two TAP-NBDs.

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Funktion der Antigen‐Transportmaschinerie TAP im zellulären Immunsystem

Beismann-Driemeyer

Tampé

2004

Angewandte Chemie

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Das Immunsystem besteht aus unterschiedlichen Typen von Zellen und Molekülen, deren komplexe Wechselwirkungen ein effizientes System zur Verteidigung eines Individuums gegen eindringende Pathogene und gegen eigene transformierte Zellen bilden. Angeborene Immunität bezeichnet die sofortige Reaktion auf Mikroorganismen, unabhängig von der Art des Eindringlings. Erworbene Immunität dagegen ruft eine spezifische Immunantwort hervor, wodurch das Individuum vor Fremdzellen von bestimmten Eindringlingen oder sogar vor Tumorzellen geschützt wird, und gibt lang anhaltenden Schutz bei wiederholter Exposition. Antikörper‐Produktion und zellvermittelte Antworten sind die zwei verzahnten Zweige des erworbenen Immunsystems. Normalerweise aktivieren auf der Zelloberfläche präsentierte antigene Peptide die zelluläre Immunantwort. Der Transportkomplex TAP hat eine Schlüsselfunktion bei der Antigenprozessierung und ‐präsentation. Dieser Aufsatz diskutiert die neuesten Forschungsergebnisse zur Struktur und zum Mechanismus sowie zu den mit Krankheiten verbundenen Fehlfunktionen des TAP‐Komplexes.

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The transporter associated with antigen processing TAP: structure and function

Cited by 56 publications

References 51 publications

Transporter Associated with Antigen Processing Preselection of Peptides Binding to the MHC: A Bioinformatic Evaluation

Transporter Associated with Antigen Processing Preselection of Peptides Binding to the MHC: A Bioinformatic Evaluation

Functional Role of C-Terminal Sequence Elements in the Transporter Associated with Antigen Processing

Funktion der Antigen‐Transportmaschinerie TAP im zellulären Immunsystem

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