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

Authors
Hilton, Hugo G.; McMurtrey, Curtis P.; Han, Alex S.; Djaoud, Zakia; Guethlein, Lisbeth A.; Blokhuis, Jeroen H.; Pugh, Jason L.; Goyos, Ana; Horowitz, Amir; Buchli, Rico; Jackson, Ken W.; Bardet, Wilfred; Bushnell, David A.; Robinson, Philip J.; Mendoza, Juan L; Birnbaum, Michael E.; Nielsen, Morten; Garcia, K. Christopher; Hildebrand, William H.; Parham, Peter
Publication Year
2017
Language
English
Format
article
Status
Published version
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.
Fil: Hilton, Hugo G.. University of Stanford; Estados Unidos
Fil: McMurtrey, Curtis P.. Oklahoma State University; Estados Unidos
Fil: Han, Alex S.. University of Stanford; Estados Unidos
Fil: Djaoud, Zakia. University of Stanford; Estados Unidos
Fil: Guethlein, Lisbeth A.. University of Stanford; Estados Unidos
Fil: Blokhuis, Jeroen H.. University of Stanford; Estados Unidos
Fil: Pugh, Jason L.. University of Stanford; Estados Unidos
Fil: Goyos, Ana. University of Stanford; Estados Unidos
Fil: Horowitz, Amir. University of Stanford; Estados Unidos
Fil: Buchli, Rico. Pure Protein LLC; Estados Unidos
Fil: Jackson, Ken W.. Oklahoma State University; Estados Unidos
Fil: Bardet, Wilfred. Oklahoma State University; Estados Unidos
Fil: Bushnell, David A.. University of Stanford; Estados Unidos
Fil: Robinson, Philip J.. University of Stanford; Estados Unidos
Fil: Mendoza, Juan L. University of Stanford; Estados Unidos
Fil: Birnbaum, Michael E.. University of Stanford; Estados Unidos
Fil: Nielsen, Morten. Technical University of Denmark; Dinamarca. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Garcia, K. Christopher. University of Stanford; Estados Unidos
Fil: Hildebrand, William H.. Oklahoma State University; Estados Unidos
Fil: Parham, Peter. University of Stanford; Estados Unidos
Subject
ANTIGEN PRESENTATION
GENETIC POLYMORPHISM
HLA CLASS I
HOST-PATHOGEN INTERACTIONS
KIR
MASS SPECTROMETRY
MODERN HUMAN MIGRATION
PEPTIDOME
Salud Ocupacional
Ciencias de la Salud
CIENCIAS MÉDICAS Y DE LA SALUD
Access level
Restricted access
License
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repository
CONICET Digital (CONICET)
Institution
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identifier
oai:ri.conicet.gov.ar:11336/48614