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

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

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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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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Bashirova, AA
Martin-Gayo, E
Jones, DC
Qi, Y
Apps, R
Gao, X
Burke, PS
Taylor, CJ
Rogich, J
Wolinsky, S
Bream, JH
Duggal, P
Hussain, S
Martinson, Jjmartins@pitt.eduJMARTINS
Weintrob, A
Kirk, GD
Fellay, J
Buchbinder, SP
Goedert, JJ
Deeks, SG
Pereyra, F
Trowsdale, J
Lichterfeld, M
Telenti, A
Walker, BD
Allen, RL
Carrington, M
Yu, XG
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorBarsh, Gregory S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 1 January 2014
Date Type: Publication
Journal or Publication Title: PLoS Genetics
Volume: 10
Number: 3
DOI or Unique Handle: 10.1371/journal.pgen.1004196
Schools and Programs: Graduate School of Public Health > Infectious Diseases and Microbiology
Refereed: Yes
ISSN: 1553-7390
Date Deposited: 01 Jul 2014 16:13
Last Modified: 02 Feb 2019 16:57
URI: http://d-scholarship.pitt.edu/id/eprint/22120

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