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HLA-II immunopeptidome profiling and deep learning reveal features of antigenicity to inform antigen discovery

ABSTRACT: Strazar M, Park J, Abelin JG, Taylor HB, Pedersen TK, Plichta DR, Brown EM, Eraslan B, Ortiz K, Clauser KR, Carr SA, Xavier RJ, Graham DB. 2022. T cell responses are exquisitely antigen-specific and directed against peptide epitopes displayed by human leukocyte antigen (HLA) on the surface of presenting cells. In particular, class II HLA (HLA-II) is remarkably polymorphic, which allows for presentation of diverse peptide antigens to T cells, but also forms the basis for genetic associations with diverse immunopathologies across the spectrum of infectious disease and autoimmunity. Here, we employ monoallelic immunopeptidomics to retrieve over 200,000 unique peptides presented by 41 HLA-II heterodimers covering major alleles across diverse ancestries. We leveraged this expansive dataset to develop computational models that predict peptide antigens based on HLA-II binding properties and infer informative features of the protein antigens from which these peptides derive. Combining both peptide and (contextual) protein features, we develop Context Aware Predictor of T cell Antigens (CAPTAn) to discover novel T cell epitopes from prokaryotes in the human microbiome and the viral pandemic pathogen SARS-CoV-2.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Bifidobacterium Longum (ncbitaxon:216816) Veillonella Parvula (ncbitaxon:29466) Clostridium Clostridioforme 90a1 (ncbitaxon:999403) Bacteroides Thetaiotaomicron (ncbitaxon:818) Homo Sapiens (ncbitaxon:9606) Akkermansia Muciniphila (ncbitaxon:239935) Ruminococcus Gnavus Atcc 29149 (ncbitaxon:411470)

SUBMITTER: Steven A. Carr

PROVIDER: MSV000089225 | MassIVE | Fri Apr 08 06:04:00 BST 2022

SECONDARY ACCESSION(S): PXD033106

REPOSITORIES: MassIVE

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