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

被引：36

作者：

Hilton, Hugo G. ^{[1
,2
]}

McMurtrey, Curtis P. ^{[3
]}

Han, Alex S. ^{[1
,2
]}

Djaoud, Zakia ^{[1
,2
]}

Guethlein, Lisbeth A. ^{[1
,2
]}

Blokhuis, Jeroen H. ^{[1
,2
]}

Pugh, Jason L. ^{[1
,2
]}

Goyos, Ana ^{[1
,2
]}

Horowitz, Amir ^{[1
,2
]}

Buchli, Rico ^{[4
]}

Jackson, Ken W. ^{[3
]}

Bardet, Wilfred ^{[3
]}

Bushnell, David A. ^{[1
]}

Robinson, Philip J. ^{[1
]}

Mendoza, Juan L. ^{[1
,5
]}

Birnbaum, Michael E. ^{[1
,5
]}

Nielsen, Morten ^{[6
,7
]}

Garcia, K. Christopher ^{[1
,5
]}

Hildebrand, William H. ^{[3
]}

Parham, Peter ^{[1
,2
]}

机构：

[1] Stanford Univ, Sch Med, Dept Struct Biol, Stanford, CA 94305 USA

[2] Stanford Univ, Dept Microbiol & Immunol, Sch Med, Stanford, CA 94305 USA

[3] Univ Oklahoma, Hlth Sci Ctr, Dept Microbiol & Immunol, Oklahoma City, OK 73104 USA

[4] Pure Prot LLC, Oklahoma City, OK 73104 USA

[5] Stanford Univ, Sch Med, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA

[6] Tech Univ Denmark, Dept Bio & Hlth Informat, DK-2800 Lyngby, Denmark

[7] Univ Nacl San Martin, Inst Invest Biotecnol, Buenos Aires, DF, Argentina

来源：

CELL REPORTS | 2017年 / 19卷 / 07期

关键词：

MHC CLASS-I; IMMUNOGLOBULIN-LIKE RECEPTOR; HLA-C EXPRESSION; T-CELL EPITOPES; CRYSTAL-STRUCTURE; GRAVES-DISEASE; SURFACE EXPRESSION; LEPROSY PATIENTS; BINDING-SITE; ASSOCIATION;

D O I：

10.1016/j.celrep.2017.04.059

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：1394 / 1405

页数：12

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