The Intergenic Recombinant HLA-B∗46:01 Has a Distinctive Peptidome that Includes KIR2DL3 Ligands

Cell Reports
Hugo G HiltonPeter Parham

Abstract

HLA-B∗46:01 was formed by an intergenic mini-conversion, between HLA-B∗15:01 and HLA-C∗01:02, in Southeast Asia during the last 50,000 years, and it has since become the most common HLA-B allele in the region. A functional effect of the mini-conversion was introduction of the C1 epitope into HLA-B∗46:01, making it an exceptional HLA-B allotype that is recognized by the C1-specific natural killer (NK) cell receptor KIR2DL3. High-resolution mass spectrometry showed that HLA-B∗46:01 has a low-diversity peptidome that is distinct from those of its parents. A minority (21%) of HLA-B∗46:01 peptides, with common C-terminal characteristics, form ligands for KIR2DL3. The HLA-B∗46:01 peptidome is predicted to be enriched for peptide antigens derived from Mycobacterium leprae. Overall, the results indicate that the distinctive peptidome and functions of HLA-B∗46:01 provide carriers with resistance to leprosy, which drove its rapid rise in frequency in Southeast Asia.

Citations

Feb 3, 2018·Annual Review of Immunology·Peter Parham, Lisbeth A Guethlein
Jul 30, 2017·Immunology·Francesco Colucci, James Traherne
Nov 16, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·David GfellerMichal Bassani-Sternberg
Sep 4, 2019·HLA : Immune Response Genetics·Shayne LoubserCaroline T Tiemessen
Jun 12, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Monojit DebnathMichael Berk
Jul 12, 2017·Immunogenetics·Hugo G Hilton, Peter Parham
May 2, 2018·Proceedings of the National Academy of Sciences of the United States of America·Philippe GuillaumeDavid Gfeller
Aug 10, 2018·Frontiers in Immunology·David Gfeller, Michal Bassani-Sternberg
Nov 10, 2018·Nature Communications·Patricia T IllingAnthony W Purcell
Sep 25, 2017·Scientific Reports·Susanna J DunachieRosemary J Boyton
Aug 14, 2021·Frontiers in Immunology·Angeliki G VittorakiIoannis Theodorou
Sep 8, 2021·Physiological Genomics·Nidhi ShuklaPrashanth Suravajhala

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Methods Mentioned

BETA
PCA
flow cytometry
Assay

Software Mentioned

custom R script
custom Perl
MATLAB
WebLogo
ArcGIS
GraphPad Prism
NNAlign
NetMHC

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