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BIITE: A Tool to Determine HLA Class II Epitopes from T Cell ELISpot Data

Lookup NU author(s): Emeritus Professor John Robinson

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

Activation of CD4(+) T cells requires the recognition of peptides that are presented by HLA class II molecules and can be assessed experimentally using the ELISpot assay. However, even given an individual's HLA class II genotype, identifying which class II molecule is responsible for a positive ELISpot response to a given peptide is not trivial. The two main difficulties are the number of HLA class II molecules that can potentially be formed in a single individual (3-14) and the lack of clear peptide binding motifs for class II molecules. Here, we present a Bayesian framework to interpret ELISpot data (BIITE: Bayesian Immunogenicity Inference Tool for ELISpot); specifically BIITE identifies which HLA-II: peptide combination(s) are immunogenic based on cohort ELISpot data. We apply BIITE to two ELISpot datasets and explore the expected performance using simulations. We show this method can reach high accuracies, depending on the cohort size and the success rate of the ELISpot assay within the cohort.


Publication metadata

Author(s): Boelen L, O'Neill PK, Quigley KJ, Reynolds CJ, Maillere B, Robinson JH, Lertmemongkolchai G, Altmann DM, Boyton RJ, Asquith B

Publication type: Article

Publication status: Published

Journal: PLoS Computational Biology

Year: 2016

Volume: 12

Issue: 3

Online publication date: 08/03/2016

Acceptance date: 08/02/2016

Date deposited: 21/07/2016

ISSN (print): 1553-734X

ISSN (electronic): 1553-7358

Publisher: Public Library of Science

URL: http://dx.doi.org/10.1371/journal.pcbi.1004796

DOI: 10.1371/journal.pcbi.1004796


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Funding

Funder referenceFunder name
MRC
15012Leukemia and Lymphoma Research
317040European Union
J007439Medical Research Council UK
G1001052Medical Research Council UK
HHSN272200900046CNational Institutes of Health (NIH)
P14475Welton Foundation

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