A Dataset of Experimental HLA-B*2705 Peptide Binding Affinities

Valerie A Walshe,Irini A Doytchinova,Darren R Flower,Channa K Hattotuwagama

doi:10.1155/2014/914684

Abstract

T-cell epitopes form the basis of many vaccines, diagnostics, and reagents. Current methods for the in silico identification of T-cell epitopes rely, in the main, on the accurate quantitative prediction of peptide-Major Histocompatibility Complex (pMHC) affinity using data-driven computational approaches. Here, we describe a dataset of experimentally determined pMHC binding affinities for the problematic human class I allele HLA-B*2705. Using an in-house, FACS-based, MHC stabilization assay, we measured binding of 223 peptides. This dataset includes both nonbinding and binding peptides, with measured affinities (expressed as −log10 of the half-maximal binding level) ranging from 1.2 to 7.4. This dataset should provide a useful independent benchmark for new and existing methods for predicting peptide binding to HLA-B*2705.

Highlights

Products of the Major Histocompatibility Complex (MHC) play a fundamental role in regulating immune responses
These were calculated as the test mean fluorescence intensity (MFI) minus the no peptide isotype control MFI divided by the no peptide HLAB∗2705-stained control MFI minus the no peptide isotype control MFI
Peptide binding to HLAB∗2705 is of undoubted importance to both autoimmune diseases and pathologies, such as spondyloarthropathies, and to infectious disease, as well as other aspects of somatic homeostasis, such as the surveillance of cancer cells

Summary

Introduction

Products of the Major Histocompatibility Complex (MHC) play a fundamental role in regulating immune responses. The role of HLA-B27-peptide binding remains critical to any convincing and compelling exegesis of spondyloarthropathies, despite the many alternative explanations provided for HLAB27 subtypes’ involvement in the pathogenesis of spondyloarthropathies [7]: (1) oxidative misfolding of HLA-B27, (2) cell surface expression of HLA-B27 homodimers, (3) β2microglobulin-free and peptide-free HLA-B27 heavy chain expression, (4) HLA-B27 modulated ERAAP and tapasin function, and (5) β2-microglobulin overexpression and/or deposition, amongst many others. Each of these mechanisms, or any combination thereof, may contribute causally to the emergence of spondyloarthropathy, yet each is itself related to peptide binding. We determined the affinities of 223 peptides binding to the MHC class I allele HLA-B∗2705 using an in-house, fluorescence-activated cell sorting- (FACS-) based, MHC stabilization assay [14,15,16,17]

Methodology

Dataset Description

Findings

Concluding Remarks