Bw4 ligand and direct T-cell receptor binding induced selection on HLA A and B alleles.
Bw4
HLA
T cell receptor
allele
balancing
machine learning
selection
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2023
2023
Historique:
received:
07
06
2023
accepted:
26
10
2023
medline:
17
12
2023
pubmed:
11
12
2023
entrez:
11
12
2023
Statut:
epublish
Résumé
The HLA region is the hallmark of balancing selection, argued to be driven by the pressure to present a wide variety of viral epitopes. As such selection on the peptide-binding positions has been proposed to drive HLA population genetics. MHC molecules also directly binds to the T-Cell Receptor and killer cell immunoglobulin-like receptors (KIR). We here combine the HLA allele frequencies in over six-million Hematopoietic Stem Cells (HSC) donors with a novel machine-learning-based method to predict allele frequency. We show for the first time that allele frequency can be predicted from their sequences. This prediction yields a natural measure for selection. The strongest selection is affecting KIR binding regions, followed by the peptide-binding cleft. The selection from the direct interaction with the KIR and TCR is centered on positively charged residues (mainly Arginine), and some positions in the peptide-binding cleft are not associated with the allele frequency, especially Tyrosine residues. These results suggest that the balancing selection for peptide presentation is combined with a positive selection for KIR and TCR binding.
Identifiants
pubmed: 38077375
doi: 10.3389/fimmu.2023.1236080
pmc: PMC10703150
doi:
Substances chimiques
Ligands
0
Receptors, KIR
0
HLA-A Antigens
0
Peptides
0
Receptors, Antigen, T-Cell
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1236080Informations de copyright
Copyright © 2023 Levi, Levi and Louzoun.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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