The Intergenic Recombinant HLA-B∗46:01 Has a Distinctive Peptidome that Includes KIR2DL3 Ligands
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∗4...
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Elsevier
2017-05-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124717305703 |
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doaj-80996e0dab9f4ff09d46ee3a014674f32020-11-24T20:40:16ZengElsevierCell Reports2211-12472017-05-011971394140510.1016/j.celrep.2017.04.059The Intergenic Recombinant HLA-B∗46:01 Has a Distinctive Peptidome that Includes KIR2DL3 LigandsHugo G. Hilton0Curtis P. McMurtrey1Alex S. Han2Zakia Djaoud3Lisbeth A. Guethlein4Jeroen H. Blokhuis5Jason L. Pugh6Ana Goyos7Amir Horowitz8Rico Buchli9Ken W. Jackson10Wilfred Bardet11David A. Bushnell12Philip J. Robinson13Juan L. Mendoza14Michael E. Birnbaum15Morten Nielsen16K. Christopher Garcia17William H. Hildebrand18Peter Parham19Department of Structural Biology, School of Medicine, Stanford University, Stanford, CA 94305, USADepartment of Microbiology & Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USADepartment of Structural Biology, School of Medicine, Stanford University, Stanford, CA 94305, USADepartment of Structural Biology, School of Medicine, Stanford University, Stanford, CA 94305, USADepartment of Structural Biology, School of Medicine, Stanford University, Stanford, CA 94305, USADepartment of Structural Biology, School of Medicine, Stanford University, Stanford, CA 94305, USADepartment of Structural Biology, School of Medicine, Stanford University, Stanford, CA 94305, USADepartment of Structural Biology, School of Medicine, Stanford University, Stanford, CA 94305, USADepartment of Structural Biology, School of Medicine, Stanford University, Stanford, CA 94305, USAPure Protein LLC, Oklahoma City, OK 73104, USADepartment of Microbiology & Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USADepartment of Microbiology & Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USADepartment of Structural Biology, School of Medicine, Stanford University, Stanford, CA 94305, USADepartment of Structural Biology, School of Medicine, Stanford University, Stanford, CA 94305, USADepartment of Structural Biology, School of Medicine, Stanford University, Stanford, CA 94305, USADepartment of Structural Biology, School of Medicine, Stanford University, Stanford, CA 94305, USADepartment of Bio and Health Informatics, Technical University of Denmark, 2800 Kgs. Lyngby, DenmarkDepartment of Structural Biology, School of Medicine, Stanford University, Stanford, CA 94305, USADepartment of Microbiology & Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USADepartment of Structural Biology, School of Medicine, Stanford University, Stanford, CA 94305, USAHLA-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.http://www.sciencedirect.com/science/article/pii/S2211124717305703HLA class IKIRantigen presentationgenetic polymorphismhost-pathogen interactionsmodern human migrationpeptidomemass spectrometry |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
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 |
| spellingShingle |
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 The Intergenic Recombinant HLA-B∗46:01 Has a Distinctive Peptidome that Includes KIR2DL3 Ligands Cell Reports HLA class I KIR antigen presentation genetic polymorphism host-pathogen interactions modern human migration peptidome mass spectrometry |
| author_facet |
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 |
| author_sort |
Hugo G. Hilton |
| title |
The Intergenic Recombinant HLA-B∗46:01 Has a Distinctive Peptidome that Includes KIR2DL3 Ligands |
| title_short |
The Intergenic Recombinant HLA-B∗46:01 Has a Distinctive Peptidome that Includes KIR2DL3 Ligands |
| title_full |
The Intergenic Recombinant HLA-B∗46:01 Has a Distinctive Peptidome that Includes KIR2DL3 Ligands |
| title_fullStr |
The Intergenic Recombinant HLA-B∗46:01 Has a Distinctive Peptidome that Includes KIR2DL3 Ligands |
| title_full_unstemmed |
The Intergenic Recombinant HLA-B∗46:01 Has a Distinctive Peptidome that Includes KIR2DL3 Ligands |
| title_sort |
intergenic recombinant hla-b∗46:01 has a distinctive peptidome that includes kir2dl3 ligands |
| publisher |
Elsevier |
| series |
Cell Reports |
| issn |
2211-1247 |
| publishDate |
2017-05-01 |
| description |
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. |
| topic |
HLA class I KIR antigen presentation genetic polymorphism host-pathogen interactions modern human migration peptidome mass spectrometry |
| url |
http://www.sciencedirect.com/science/article/pii/S2211124717305703 |
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