PXD023284

PXD023284 is an original dataset announced via ProteomeXchange.

Title	HLA binding of self-peptides is biased towards proteins with specific molecular functions
Description	Human leukocyte antigen (HLA) is highly polymorphic and plays a key role in guiding adaptive immune responses by presenting foreign and self peptides to T cells. Each HLA variant selects a minor fraction of peptides that match a certain motif required for optimal interaction with the peptide-binding groove. These restriction rules define the landscape of peptides presented to T cells. Given these limitations, one might suggest that the choice of peptides presented by HLA is non-random and there is preferential presentation of an array of peptides that is optimal for distinguishing self and foreign proteins. In this study we explore these preferences with a comparative analysis of self peptides enriched and depleted in HLA ligands. We show that HLAs exhibit preferences towards presenting peptides from certain proteins while disfavoring others with specific functions, and highlight differences between various HLA genes and alleles in those preferences. We link those differences to HLA anchor residue propensities and amino acid composition of preferentially presented proteins. The set of proteins that peptides presented by a given HLA are most likely to be derived from can be used to distinguish between class I and class II HLAs and HLA alleles. Our observations can be extrapolated to explain the protective effect of certain HLA alleles in infectious diseases, and we hypothesize that they can also explain susceptibility to certain autoimmune diseases and cancers. We demonstrate that these differences lead to differential presentation of HIV, influenza virus, SARS-CoV-1 and SARS-CoV-2 proteins by various HLA alleles. Finally, we show that the reported self peptidome preferences of distinct HLA variants can be compensated by combinations of HLA-A/HLA-B and HLA-A/HLA-C alleles in frequent haplotypes.
HostingRepository	PRIDE
AnnounceDate	2026-05-28
AnnouncementXML	Submission_2026-05-28_08:24:45.539.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Nicola Ternette
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2020-12-23 03:19:46	ID requested
⏵ 1	2026-05-28 08:24:46	announced

10.1101/2021.02.16.431395;

Karnaukhov V, Paes W, Woodhouse IB, Partridge T, Nicastri A, Brackenridge S, Scherbinin D, Chudakov DM, Zvyagin IV, Ternette N, Koohy H, Borrow P, Shugay M, HLA binding of self-peptides is biased towards proteins with specific molecular functions. bioRxiv, ():(2021) [pubmed]

submitter keyword: antigen presetation, peptides,HLA, LC-MS/MS

Nicola Ternette
contact affiliation	University of Oxford
contact email	nicola.ternette@ndm.ox.ac.uk
lab head
Nicola Ternette
contact affiliation	University of Oxford
contact email	nicola.ternette@ndm.ox.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD023284
     1. Label: PRIDE project
     2. Name: HLA binding of self-peptides is biased towards proteins with specific molecular functions