2. Academic Validation
  3. The Intergenic Recombinant HLA-B∗46:01 Has a Distinctive Peptidome that Includes KIR2DL3 Ligands

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

  • Cell Rep. 2017 May 16;19(7):1394-1405. doi: 10.1016/j.celrep.2017.04.059.
Hugo G Hilton 1,  Curtis P McMurtrey 2,  Alex S Han 3,  Zakia Djaoud 3,  Lisbeth A Guethlein 3,  Jeroen H Blokhuis 3,  Jason L Pugh 3,  Ana Goyos 3,  Amir Horowitz 3,  Rico Buchli 4,  Ken W Jackson 2,  Wilfred Bardet 2,  David A Bushnell 5,  Philip J Robinson 5,  Juan L Mendoza 6,  Michael E Birnbaum 6,  Morten Nielsen 7,  K Christopher Garcia 6,  William H Hildebrand 2,  Peter Parham 3
Affiliations

Affiliations

  • 1 Department of Structural Biology, School of Medicine, Stanford University, Stanford, CA 94305, USA; Department of Microbiology & Immunology, School of Medicine, Stanford University, Stanford, CA 94305, USA. Electronic address: hghhilton@gmail.com.
  • 2 Department of Microbiology & Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
  • 3 Department of Structural Biology, School of Medicine, Stanford University, Stanford, CA 94305, USA; Department of Microbiology & Immunology, School of Medicine, Stanford University, Stanford, CA 94305, USA.
  • 4 Pure Protein LLC, Oklahoma City, OK 73104, USA.
  • 5 Department of Structural Biology, School of Medicine, Stanford University, Stanford, CA 94305, USA.
  • 6 Department of Structural Biology, School of Medicine, Stanford University, Stanford, CA 94305, USA; Department of Molecular & Cellular Physiology, School of Medicine, Stanford University, Stanford, CA 94305, USA.
  • 7 Department of Bio and Health Informatics, Technical University of Denmark, 2800 Kgs. Lyngby, Denmark; Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín, Buenos Aires, Argentina.
PMID: 28514659 DOI: 10.1016/j.celrep.2017.04.059
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.

Keywords

HLA class I; KIR; antigen presentation; genetic polymorphism; host-pathogen interactions; mass spectrometry; modern human migration; peptidome.

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