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

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Author
Bashirova, Arman A.
Martin-Gayo, Enrique
Jones, Des C.
Qi, Ying
Apps, Richard
Gao, Xiaojiang
Burke, Patrick S.
Taylor, Craig J.
Rogich, Jerome
Wolinsky, Steven
Bream, Jay H.
Duggal, Priya
Hussain, Shehnaz
Martinson, Jeremy
Weintrob, Amy
Kirk, Gregory D.
Fellay, Jacques
Buchbinder, Susan P.
Goedert, James J.
Deeks, Steven G.
Pereyra, Florencia
Trowsdale, John
Telenti, Amalio
Allen, Rachel L.
Carrington, Mary
Yu, Xu G.
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1371/journal.pgen.1004196Metadata
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Bashirova, A. A., E. Martin-Gayo, D. C. Jones, Y. Qi, R. Apps, X. Gao, P. S. Burke, et al. 2014. “LILRB2 Interaction with HLA Class I Correlates with Control of HIV-1 Infection.” PLoS Genetics 10 (3): e1004196. doi:10.1371/journal.pgen.1004196. http://dx.doi.org/10.1371/journal.pgen.1004196.Abstract
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.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3945438/pdf/Terms of Use
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