relation: http://d-scholarship-dev.library.pitt.edu/22120/
title: LILRB2 Interaction with HLA Class I Correlates with Control of HIV-1 Infection
creator: Bashirova, AA
creator: Martin-Gayo, E
creator: Jones, DC
creator: Qi, Y
creator: Apps, R
creator: Gao, X
creator: Burke, PS
creator: Taylor, CJ
creator: Rogich, J
creator: Wolinsky, S
creator: Bream, JH
creator: Duggal, P
creator: Hussain, S
creator: Martinson, J
creator: Weintrob, A
creator: Kirk, GD
creator: Fellay, J
creator: Buchbinder, SP
creator: Goedert, JJ
creator: Deeks, SG
creator: Pereyra, F
creator: Trowsdale, J
creator: Lichterfeld, M
creator: Telenti, A
creator: Walker, BD
creator: Allen, RL
creator: Carrington, M
creator: Yu, XG
description: 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.
date: 2014-01-01
type: Article
type: PeerReviewed
format: application/pdf
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/22120/1/journal.pgen.1004196.pdf
format: text/plain
language: en
rights: attached
identifier: http://d-scholarship-dev.library.pitt.edu/22120/8/licence.txt
identifier:   Bashirova, AA and Martin-Gayo, E and Jones, DC and Qi, Y and Apps, R and Gao, X and Burke, PS and Taylor, CJ and Rogich, J and Wolinsky, S and Bream, JH and Duggal, P and Hussain, S and Martinson, J and Weintrob, A and Kirk, GD and Fellay, J and Buchbinder, SP and Goedert, JJ and Deeks, SG and Pereyra, F and Trowsdale, J and Lichterfeld, M and Telenti, A and Walker, BD and Allen, RL and Carrington, M and Yu, XG  (2014) LILRB2 Interaction with HLA Class I Correlates with Control of HIV-1 Infection.  PLoS Genetics, 10 (3).   ISSN 1553-7390     
relation: 10.1371/journal.pgen.1004196