02196nas a2200469   4500000000100000008004100001653001200042653001600054653000800070653002500078653002500103653003100128653002200159653002700181653001400208100001400222700001600236700001000252700001300262700001600275700001600291700001100307700001200318700001500330700001300345700001500358700001300373700001500386700001600401700001400417700001500431700001400446700001400460700001700474700001300491245010400504856006700608300001400675490000700689520101600696022001401712       2017                            d10aleprosy10aHLA class I10aKIR10aAntigen Presentation10aGenetic polymorphism10aHost-Pathogen Interactions10aMass Spectrometry10aModern human migration10aPeptidome1 aHilton HG1 aMcMurtrey C1 aHan A1 aDjaoud Z1 aGuethlein L1 aBlokhuis JH1 aPugh J1 aGoyos A1 aHorowitz A1 aBuchli R1 aJackson KW1 aBardet W1 aBushnell D1 aRobinson PJ1 aMendoza J1 aBirnbaum M1 aNielsen M1 aGarcia CK1 aHildebrand W1 aParham P00aThe Intergenic Recombinant HLA-B∗46:01 Has a Distinctive Peptidome that Includes KIR2DL3 Ligands.  uhttp://www.cell.com/cell-reports/pdf/S2211-1247(17)30570-3.pdf  a1394-14050 v193 a<p>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.</p>
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