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

Hugo G. Hilton; Curtis P. McMurtrey; Alex S. Han; Zakia Djaoud; Lisbeth A. Guethlein; Jeroen H. Blokhuis; Jason L. Pugh; Ana Goyos; Amir Horowitz; Rico Buchli; Ken W. Jackson; Wilfred Bardet; David A. Bushnell; Philip J. Robinson; Juan L. Mendoza; Michael E. Birnbaum; Morten Nielsen; K. Christopher Garcia; William H. Hildebrand; Peter Parham

doi:10.1016/j.celrep.2017.04.059

Cell Reports (May 2017)

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

Hugo G. Hilton,
Curtis P. McMurtrey,
Alex S. Han,
Zakia Djaoud,
Lisbeth A. Guethlein,
Jeroen H. Blokhuis,
Jason L. Pugh,
Ana Goyos,
Amir Horowitz,
Rico Buchli,
Ken W. Jackson,
Wilfred Bardet,
David A. Bushnell,
Philip J. Robinson,
Juan L. Mendoza,
Michael E. Birnbaum,
Morten Nielsen,
K. Christopher Garcia,
William H. Hildebrand,
Peter Parham

Affiliations

Hugo G. Hilton: Department of Structural Biology, School of Medicine, Stanford University, Stanford, CA 94305, USA
Curtis P. McMurtrey: Department of Microbiology & Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
Alex S. Han: Department of Structural Biology, School of Medicine, Stanford University, Stanford, CA 94305, USA
Zakia Djaoud: Department of Structural Biology, School of Medicine, Stanford University, Stanford, CA 94305, USA
Lisbeth A. Guethlein: Department of Structural Biology, School of Medicine, Stanford University, Stanford, CA 94305, USA
Jeroen H. Blokhuis: Department of Structural Biology, School of Medicine, Stanford University, Stanford, CA 94305, USA
Jason L. Pugh: Department of Structural Biology, School of Medicine, Stanford University, Stanford, CA 94305, USA
Ana Goyos: Department of Structural Biology, School of Medicine, Stanford University, Stanford, CA 94305, USA
Amir Horowitz: Department of Structural Biology, School of Medicine, Stanford University, Stanford, CA 94305, USA
Rico Buchli: Pure Protein LLC, Oklahoma City, OK 73104, USA
Ken W. Jackson: Department of Microbiology & Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
Wilfred Bardet: Department of Microbiology & Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
David A. Bushnell: Department of Structural Biology, School of Medicine, Stanford University, Stanford, CA 94305, USA
Philip J. Robinson: Department of Structural Biology, School of Medicine, Stanford University, Stanford, CA 94305, USA
Juan L. Mendoza: Department of Structural Biology, School of Medicine, Stanford University, Stanford, CA 94305, USA
Michael E. Birnbaum: Department of Structural Biology, School of Medicine, Stanford University, Stanford, CA 94305, USA
Morten Nielsen: Department of Bio and Health Informatics, Technical University of Denmark, 2800 Kgs. Lyngby, Denmark
K. Christopher Garcia: Department of Structural Biology, School of Medicine, Stanford University, Stanford, CA 94305, USA
William H. Hildebrand: Department of Microbiology & Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
Peter Parham: Department of Structural Biology, School of Medicine, Stanford University, Stanford, CA 94305, USA

DOI: https://doi.org/10.1016/j.celrep.2017.04.059
Journal volume & issue: Vol. 19, no. 7
pp. 1394 – 1405

Abstract

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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.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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