TY - JOUR KW - leprosy KW - HLA class I KW - KIR KW - Antigen Presentation KW - Genetic polymorphism KW - Host-Pathogen Interactions KW - Mass Spectrometry KW - Modern human migration KW - Peptidome AU - Hilton HG AU - McMurtrey C AU - Han A AU - Djaoud Z AU - Guethlein L AU - Blokhuis JH AU - Pugh J AU - Goyos A AU - Horowitz A AU - Buchli R AU - Jackson KW AU - Bardet W AU - Bushnell D AU - Robinson PJ AU - Mendoza J AU - Birnbaum M AU - Nielsen M AU - Garcia CK AU - Hildebrand W AU - Parham P AB -

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.

BT - Cell reports C1 -

http://www.ncbi.nlm.nih.gov/pubmed/28514659?dopt=Abstract

DO - 10.1016/j.celrep.2017.04.059 IS - 7 J2 - Cell Rep LA - eng N2 -

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.

PY - 2017 SP - 1394 EP - 1405 T2 - Cell reports TI - The Intergenic Recombinant HLA-B∗46:01 Has a Distinctive Peptidome that Includes KIR2DL3 Ligands. UR - http://www.cell.com/cell-reports/pdf/S2211-1247(17)30570-3.pdf VL - 19 SN - 2211-1247 ER -