Relationship between peptide selectivities of human transporters associated with antigen processing and HLA class I molecules

Soizic Daniel, Vladimir Brusic, Sophie Caillat-Zucman, Nicolai Petrovsky, Leonard Harrison, Daniela Riganelli, Francesco Sinigaglia, Fabio Gallazzi, Jürgen Hammer, Peter M. Van Endert

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

Efficiency of presentation of a peptide epitope by a MHC class I molecule depends on two parameters: its binding to the MHC molecule and its generation by intracellular Ag processing. In contrast to the former parameter, the mechanisms underlying peptide selection in Ag processing are poorly understood. Peptide translocation by the TAP transporter is required for presentation of most epitopes and may modulate peptide supply to MHC class I molecules. To study the role of human TAP for peptide presentation by individual HLA class I molecules, we generated artificial neural networks capable of predicting the affinity of TAP for random sequence 9-mer peptides. Using neural network-based predictions of TAP affinity, we found that peptides eluted from three different HLA class I molecules had higher TAP affinities than control peptides with equal binding affinities for the same HLA class I molecules, suggesting that human TAP may contribute to epitope selection. In simulated TAP binding experiments with 408 HLA class I binding peptides, HLA class I molecules differed significantly wit respect to TAP affinities of their ligands. As a result, some class I molecules, especially HLA-B27, may be particularly efficient in presentation of cytosolic peptides with low concentrations, while most class I molecules may predominantly present abundant cytosolic peptides.

Original languageEnglish
Pages (from-to)617-624
Number of pages8
JournalJournal of Immunology
Volume161
Issue number2
Publication statusPublished - Jul 15 1998
Externally publishedYes

Fingerprint

Antigen Presentation
Peptides
Epitopes
trypsinogen activation peptide
HLA-B27 Antigen
Wit and Humor
Ligands

ASJC Scopus subject areas

  • Immunology

Cite this

Daniel, S., Brusic, V., Caillat-Zucman, S., Petrovsky, N., Harrison, L., Riganelli, D., ... Van Endert, P. M. (1998). Relationship between peptide selectivities of human transporters associated with antigen processing and HLA class I molecules. Journal of Immunology, 161(2), 617-624.

Relationship between peptide selectivities of human transporters associated with antigen processing and HLA class I molecules. / Daniel, Soizic; Brusic, Vladimir; Caillat-Zucman, Sophie; Petrovsky, Nicolai; Harrison, Leonard; Riganelli, Daniela; Sinigaglia, Francesco; Gallazzi, Fabio; Hammer, Jürgen; Van Endert, Peter M.

In: Journal of Immunology, Vol. 161, No. 2, 15.07.1998, p. 617-624.

Research output: Contribution to journalArticle

Daniel, S, Brusic, V, Caillat-Zucman, S, Petrovsky, N, Harrison, L, Riganelli, D, Sinigaglia, F, Gallazzi, F, Hammer, J & Van Endert, PM 1998, 'Relationship between peptide selectivities of human transporters associated with antigen processing and HLA class I molecules', Journal of Immunology, vol. 161, no. 2, pp. 617-624.
Daniel S, Brusic V, Caillat-Zucman S, Petrovsky N, Harrison L, Riganelli D et al. Relationship between peptide selectivities of human transporters associated with antigen processing and HLA class I molecules. Journal of Immunology. 1998 Jul 15;161(2):617-624.
Daniel, Soizic ; Brusic, Vladimir ; Caillat-Zucman, Sophie ; Petrovsky, Nicolai ; Harrison, Leonard ; Riganelli, Daniela ; Sinigaglia, Francesco ; Gallazzi, Fabio ; Hammer, Jürgen ; Van Endert, Peter M. / Relationship between peptide selectivities of human transporters associated with antigen processing and HLA class I molecules. In: Journal of Immunology. 1998 ; Vol. 161, No. 2. pp. 617-624.
@article{3db5365358694ff982c1d7c018e1fba9,
title = "Relationship between peptide selectivities of human transporters associated with antigen processing and HLA class I molecules",
abstract = "Efficiency of presentation of a peptide epitope by a MHC class I molecule depends on two parameters: its binding to the MHC molecule and its generation by intracellular Ag processing. In contrast to the former parameter, the mechanisms underlying peptide selection in Ag processing are poorly understood. Peptide translocation by the TAP transporter is required for presentation of most epitopes and may modulate peptide supply to MHC class I molecules. To study the role of human TAP for peptide presentation by individual HLA class I molecules, we generated artificial neural networks capable of predicting the affinity of TAP for random sequence 9-mer peptides. Using neural network-based predictions of TAP affinity, we found that peptides eluted from three different HLA class I molecules had higher TAP affinities than control peptides with equal binding affinities for the same HLA class I molecules, suggesting that human TAP may contribute to epitope selection. In simulated TAP binding experiments with 408 HLA class I binding peptides, HLA class I molecules differed significantly wit respect to TAP affinities of their ligands. As a result, some class I molecules, especially HLA-B27, may be particularly efficient in presentation of cytosolic peptides with low concentrations, while most class I molecules may predominantly present abundant cytosolic peptides.",
author = "Soizic Daniel and Vladimir Brusic and Sophie Caillat-Zucman and Nicolai Petrovsky and Leonard Harrison and Daniela Riganelli and Francesco Sinigaglia and Fabio Gallazzi and J{\"u}rgen Hammer and {Van Endert}, {Peter M.}",
year = "1998",
month = "7",
day = "15",
language = "English",
volume = "161",
pages = "617--624",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "2",

}

TY - JOUR

T1 - Relationship between peptide selectivities of human transporters associated with antigen processing and HLA class I molecules

AU - Daniel, Soizic

AU - Brusic, Vladimir

AU - Caillat-Zucman, Sophie

AU - Petrovsky, Nicolai

AU - Harrison, Leonard

AU - Riganelli, Daniela

AU - Sinigaglia, Francesco

AU - Gallazzi, Fabio

AU - Hammer, Jürgen

AU - Van Endert, Peter M.

PY - 1998/7/15

Y1 - 1998/7/15

N2 - Efficiency of presentation of a peptide epitope by a MHC class I molecule depends on two parameters: its binding to the MHC molecule and its generation by intracellular Ag processing. In contrast to the former parameter, the mechanisms underlying peptide selection in Ag processing are poorly understood. Peptide translocation by the TAP transporter is required for presentation of most epitopes and may modulate peptide supply to MHC class I molecules. To study the role of human TAP for peptide presentation by individual HLA class I molecules, we generated artificial neural networks capable of predicting the affinity of TAP for random sequence 9-mer peptides. Using neural network-based predictions of TAP affinity, we found that peptides eluted from three different HLA class I molecules had higher TAP affinities than control peptides with equal binding affinities for the same HLA class I molecules, suggesting that human TAP may contribute to epitope selection. In simulated TAP binding experiments with 408 HLA class I binding peptides, HLA class I molecules differed significantly wit respect to TAP affinities of their ligands. As a result, some class I molecules, especially HLA-B27, may be particularly efficient in presentation of cytosolic peptides with low concentrations, while most class I molecules may predominantly present abundant cytosolic peptides.

AB - Efficiency of presentation of a peptide epitope by a MHC class I molecule depends on two parameters: its binding to the MHC molecule and its generation by intracellular Ag processing. In contrast to the former parameter, the mechanisms underlying peptide selection in Ag processing are poorly understood. Peptide translocation by the TAP transporter is required for presentation of most epitopes and may modulate peptide supply to MHC class I molecules. To study the role of human TAP for peptide presentation by individual HLA class I molecules, we generated artificial neural networks capable of predicting the affinity of TAP for random sequence 9-mer peptides. Using neural network-based predictions of TAP affinity, we found that peptides eluted from three different HLA class I molecules had higher TAP affinities than control peptides with equal binding affinities for the same HLA class I molecules, suggesting that human TAP may contribute to epitope selection. In simulated TAP binding experiments with 408 HLA class I binding peptides, HLA class I molecules differed significantly wit respect to TAP affinities of their ligands. As a result, some class I molecules, especially HLA-B27, may be particularly efficient in presentation of cytosolic peptides with low concentrations, while most class I molecules may predominantly present abundant cytosolic peptides.

UR - http://www.scopus.com/inward/record.url?scp=0032528406&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032528406&partnerID=8YFLogxK

M3 - Article

C2 - 9670935

AN - SCOPUS:0032528406

VL - 161

SP - 617

EP - 624

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 2

ER -