LILRB2 Interaction with HLA Class I Correlates with Control of HIV-1 Infection

被引：71

作者：

Bashirova, Arman A. ^{[1
,2
]}

Martin-Gayo, Enrique ^{[2
]}

Jones, Des C. ^{[3
]}

Qi, Ying ^{[1
]}

Apps, Richard ^{[1
]}

Gao, Xiaojiang ^{[1
]}

Burke, Patrick S. ^{[2
]}

Taylor, Craig J. ^{[4
]}

Rogich, Jerome ^{[2
]}

Wolinsky, Steven ^{[5
]}

Bream, Jay H. ^{[6
]}

Duggal, Priya ^{[6
]}

Hussain, Shehnaz ^{[7
]}

Martinson, Jeremy ^{[8
]}

Weintrob, Amy ^{[9
]}

Kirk, Gregory D. ^{[10
]}

Fellay, Jacques ^{[11
]}

Buchbinder, Susan P. ^{[12
]}

Goedert, James J. ^{[13
]}

Deeks, Steven G. ^{[14
]}

Pereyra, Florencia ^{[2
,15
]}

Trowsdale, John ^{[3
]}

Lichterfeld, Mathias ^{[16
]}

Telenti, Amalio ^{[17
,18
]}

Walker, Bruce D. ^{[2
,19
]}

Allen, Rachel L. ^{[20
]}

Carrington, Mary ^{[1
,2
]}

Yu, Xu G. ^{[2
]}

机构：

[1] Leidos Biomed Res Inc, Canc & Inflammat Program, Expt Immunol Lab, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA

[2] Ragon Inst MGH MIT & Harvard, Boston, MA USA

[3] Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England

[4] Addenbrookes Hosp, Tissue Typing Labs, Cambridge, England

[5] Northwestern Univ, Sch Med, Chicago, IL USA

[6] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD USA

[7] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Los Angeles, CA USA

[8] Univ Pittsburgh, Pittsburgh, PA USA

[9] USU Infect Dis Clin Res Program, Bethesda, MD USA

[10] Johns Hopkins Univ, Sch Publ Hlth, Baltimore, MD USA

[11] Ecole Polytech Fed Lausanne, Sch Life Sci, Lausanne, Switzerland

[12] San Francisco Dept Publ Hlth, San Francisco, CA USA

[13] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA

[14] Univ Calif San Francisco, Sch Med, San Francisco, CA USA

[15] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA

[16] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA

[17] Univ Lausanne Hosp, Inst Microbiol, Lausanne, Switzerland

[18] Univ Lausanne, Lausanne, Switzerland

[19] Howard Hughes Med Inst, Chevy Chase, MD USA

[20] Univ London, St Georges Med Sch, London, England

来源：

PLOS GENETICS | 2014年 / 10卷 / 03期

基金：

瑞士国家科学基金会; 英国惠康基金;

关键词：

MHC CLASS-I; INHIBITORY RECEPTOR; DENDRITIC CELLS; MYELOMONOCYTIC CELLS; HOST CONTROL; MOLECULES; AIDS; COMPLEX; BINDING; ILT4;

D O I：

10.1371/journal.pgen.1004196

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Natural progression of HIV-1 infection depends on genetic variation in the human major histocompatibility complex (MHC) class I locus, and the CD8(+) T cell response is thought to be a primary mechanism of this effect. However, polymorphism within the MHC may also alter innate immune activity against human immunodeficiency virus type 1 (HIV-1) by changing interactions of human leukocyte antigen (HLA) class I molecules with leukocyte immunoglobulin-like receptors (LILR), a group of immunoregulatory receptors mainly expressed on myelomonocytic cells including dendritic cells (DCs). We used previously characterized HLA allotype-specific binding capacities of LILRB1 and LILRB2 as well as data from a large cohort of HIV-1-infected individuals (N = 5126) to test whether LILR-HLA class I interactions influence viral load in HIV-1 infection. Our analyses in persons of European descent, the largest ethnic group examined, show that the effect of HLA-B alleles on HIV-1 control correlates with the binding strength between corresponding HLA-B allotypes and LILRB2 (p = 10(-2)). Moreover, overall binding strength of LILRB2 to classical HLA class I allotypes, defined by the HLA-A/B/C genotypes in each patient, positively associates with viral replication in the absence of therapy in patients of both European (p = 10(-11)-10(-9)) and African (p = 10(-5)-10(-3)) descent. This effect appears to be driven by variations in LILRB2 binding affinities to HLA-B and is independent of individual class I allelic effects that are not related to the LILRB2 function. Correspondingly, in vitro experiments suggest that strong LILRB2-HLA binding negatively affects antigen-presenting properties of DCs. Thus, we propose an impact of LILRB2 on HIV-1 disease outcomes through altered regulation of DCs by LILRB2-HLA engagement.

引用

页数：10

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