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LILRB2 interaction with HLA class I correlates with control of HIV-1 infection.

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
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, Lichterfeld Mathias, Telenti Amalio, Walker Bruce D,
Project Swiss HIV Cohort Study (SHCS)
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Original article (peer-reviewed)

Journal PLoS genetics
Volume (Issue) 10(3)
Page(s) 1004196 - 1004196
Title of proceedings PLoS genetics
DOI 10.1371/journal.pgen.1004196

Open Access

URL http://doi.org/10.1371/journal.pgen.1004196
Type of Open Access Publisher (Gold Open Access)

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.
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