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

Daniel, S, Brusic, V, Caillat-Zucman, S, Petrovsky, N, Harrison, L, Riganelli, D, Sinigaglia, F, Gallazzi, F, Hammer, J and van Endert, PM (1998) Relationship between peptide selectivities of human transporters associated with antigen processing and HLA class I molecules. Journal of Immunology, 161 2: 617-624.

Author Daniel, S
Brusic, V
Caillat-Zucman, S
Petrovsky, N
Harrison, L
Riganelli, D
Sinigaglia, F
Gallazzi, F
Hammer, J
van Endert, PM
Title Relationship between peptide selectivities of human transporters associated with antigen processing and HLA class I molecules
Journal name Journal of Immunology   Check publisher's open access policy
ISSN 0022-1767
Publication date 1998-01-01
Sub-type Article (original research)
Open Access Status Not yet assessed
Volume 161
Issue 2
Start page 617
End page 624
Total pages 8
Language eng
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 with 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.
Keyword Immunology
Endoplasmic-reticulum
Surface Expression
Cell-surface
Binding
Translocation
Tap
Specificity
Variants
Mouse
Rat
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Agriculture and Food Sciences
 
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Created: Mon, 13 Aug 2007, 20:31:55 EST