Systemic inhibition of myeloid dendritic cells by circulating HLA class I molecules in HIV-1 infection

ABSTRACT The setpoint of viral RNA concentration (viral load [VL]) during chronic human immunodeficiency virus type 1 (HIV-1) infection reflects a virus-host equilibration closely related to CD8+ cytotoxic T-lymphocyte (CTL) responses, which rely heavily on antigen presentation by the human major histocompatibility complex (MHC) (i.e., HLA) class I molecules. Differences in HIV-1 VL among 259 mostly clade C virus-infected individuals (137 females and 122 males) in the Zambia-UAB HIV Research Project (ZUHRP) were associated with several HLA class I alleles and haplotypes. In particular, general linear model analyses revealed lower log10 VL among those with HLA allele B*57 (P = 0.002 [without correction]) previously implicated in favorable response and in those with HLA B*39 and A*30-Cw*03 (P = 0.002 to 0.016); the same analyses also demonstrated higher log10 VL among individuals with A*02-Cw*16, A*23-B*14, and A*23-Cw*07 (P = 0.010 to 0.033). These HLA effects remained strong (P = 0.0002 to 0.075) after adjustment for age, gender, and duration of infection and persisted across three orders of VL categories (P = 0.001 to 0.084). In contrast, neither B*35 (n = 15) nor B*53 (n = 53) showed a clear disadvantage such as that reported elsewhere for these closely related alleles. Other HLA associations with unusually high (A*68, B*41, B*45, and Cw*16) or low (B*13, Cw*12, and Cw*18) VL were either unstable or reflected their tight linkage respecting disequilibria with other class I variants. The three consistently favorable HLA class I variants retained in multivariable models and in alternative analyses were present in 30.9% of subjects with the lowest (<10,000 copies per ml) and 3.1% of those with the highest (>100,000) VL. Clear differential distribution of HLA profiles according to level of viremia suggests important host genetic contribution to the pattern of immune control and escape during HIV-1 infection.

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Effects of HIV-1 Tat on Expression of HLA Class I Molecules

Journal of Acquired Immune Deficiency Syndromes & Human Retrovirology ◽

10.1097/00042560-199603010-00003 ◽

1996 ◽

Vol 11 (3) ◽

pp. 233-240 ◽

Cited By ~ 22

Author(s):

Masanori Matsui ◽

Robert J. Warburton ◽

Patricia C. Cogswell ◽

Albert S. Baldwin ◽

Jeffrey A. Frelinger

Keyword(s):

Hla Class I ◽

Class I ◽

Hla Class I Molecules ◽

Hiv 1

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Analysis of transporter associated with antigen presentation (TAP) genes polymorphisms with HIV-1 infection

Molecular and Cellular Biochemistry ◽

10.1007/s11010-019-03649-x ◽

2019 ◽

Vol 464 (1-2) ◽

pp. 65-71 ◽

Cited By ~ 1

Author(s):

Abaineh Munshea Abitew ◽

Ranbir Chander Sobti ◽

Vijay Lakshmi Sharma ◽

Ajay Wanchu

Keyword(s):

Immune Response ◽

Hla Class I ◽

Class I ◽

Control Analysis ◽

Antigenic Peptides ◽

Human Major Histocompatibility Complex ◽

Hla Class I Molecules ◽

Increased Risk ◽

Exon 11 ◽

Hiv 1

AbstractHuman leukocyte antigen (HLA) class I molecules of the human major histocompatibility complex (MHC) play an important role in modulating immune response. HLA class I molecules present antigenic peptides to CD8+ T cells and thereby play a role in the immune surveillance of cells infected with viruses. TAP1 and TAP2 are MHC-II-encoded genes necessary for the generation of a cellular immune response and polymorphism of these genes can influence the specificity of peptides preferentially presented by the MHC class I molecules and the outcome of the immune response. Several studies implicated genetic variation in TAP genes to various immune-mediated and infectious diseases. To determine the correlation between HIV-1 infection and the TAP1 and TAP2 genes polymorphisms, we performed PCR–RFLP assay of these genes in 500 HIV-1 seropositives and the matched seronegative individuals. Statistical analysis of the data disclosed no correlation between TAP1 (C/T intron 7) gene polymorphism and HIV-1/AIDS disease. However, the current results demonstrated that the heterozygous A/G [OR (95% CI) 1.39 (1.06–1.83), P = 0.0171] and homozygous G/G [OR (95% CI) 3.38(1.56–7.46), P = 0.0010] variants of TAP2 (A/G exon 11) (T665A) gene are positively associated with an increased risk of HIV-1/AIDS infection. This case–control analysis might suggest a possible role of TAP2 (A/G exon 11) (T665A) gene in the susceptibility to HIV-1 infection and disease outcome among North Indian patients.

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Adaptive Interactions between HLA and HIV-1: Highly Divergent Selection Imposed by HLA Class I Molecules with Common Supertype Motifs

The Journal of Immunology ◽

10.4049/jimmunol.0903745 ◽

2010 ◽

Vol 184 (8) ◽

pp. 4368-4377 ◽

Cited By ~ 35

Author(s):

Mina John ◽

David Heckerman ◽

Ian James ◽

Lawrence P. Park ◽

Jonathan M. Carlson ◽

...

Keyword(s):

Hla Class I ◽

Divergent Selection ◽

Class I ◽

Hla Class I Molecules ◽

Hiv 1

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Evidence of widespread binding of HLA class I molecules to peptides.

Journal of Experimental Medicine ◽

10.1084/jem.172.3.827 ◽

1990 ◽

Vol 172 (3) ◽

pp. 827-834 ◽

Cited By ~ 40

Author(s):

J A Frelinger ◽

F M Gotch ◽

H Zweerink ◽

E Wain ◽

A J McMichael

Keyword(s):

Monoclonal Antibodies ◽

Binding Assay ◽

Solid Phase ◽

Hla Class I ◽

Class I ◽

T Cell Epitopes ◽

Single Class ◽

Hla Class I Molecules ◽

Solid Phase Binding ◽

Hiv 1

We have tested the binding of HLA class I proteins to peptides using a solid-phase binding assay. We tested 102 peptides, mostly derived from the HIV gag and HIV pol sequences. Most peptides did not bind to any class I protein tested. The pattern of binding among the three class I proteins tested, HLA-A2, -B27, and -B8, was approximately 85% concordant. Further, all five of the known HIV-1 gag T cell epitopes detected by human CTL bound at least one class I protein. Binding of class I to the peptides could be detected either by directly iodinated class I proteins, or indirectly using monoclonal antibodies specific for class I. The binding to the plates could be blocked with MA2.1, which binds in the alpha 1 region of A2, but not by W6/32, which binds elsewhere. The data presented here show that binding of class I to peptides is specific, but that many peptides bind to more than a single class I protein.

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P09-03. HLA class I alleles impact on HIV-1 disease progression by interacting with immunoregulatory HLA receptors on dendritic cells

Retrovirology ◽

10.1186/1742-4690-6-s3-p116 ◽

2009 ◽

Vol 6 (S3) ◽

Author(s):

J Huang

Keyword(s):

Dendritic Cells ◽

Disease Progression ◽

Hla Class I ◽

Class I ◽

Hiv 1

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A single CTL clone can recognize a naturally processed HIV-1 epitope presented by two different HLA class I molecules

European Journal of Immunology ◽

10.1002/1521-4141(200009)30:9<2521::aid-immu2521>3.0.co;2-q ◽

2000 ◽

Vol 30 (9) ◽

pp. 2521-2530 ◽

Cited By ~ 19

Author(s):

Hiroko Tomiyama ◽

Naoyuki Yamada ◽

Hiroki Komatsu ◽

Kazuo Hirayama ◽

Masafumi Takiguchi

Keyword(s):

Hla Class I ◽

Class I ◽

Hla Class I Molecules ◽

Hiv 1

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Soluble HLA-G Inhibits Myeloid Dendritic Cell Function in HIV-1 Infection by Interacting with Leukocyte Immunoglobulin-Like Receptor B2

Journal of Virology ◽

10.1128/jvi.01292-10 ◽

2010 ◽

Vol 84 (20) ◽

pp. 10784-10791 ◽

Cited By ~ 31

Author(s):

Jinghe Huang ◽

Patrick Burke ◽

Yue Yang ◽

Katherine Seiss ◽

Jill Beamon ◽

...

Keyword(s):

Dendritic Cells ◽

Cell Function ◽

Critical Role ◽

Antigen Presenting Cells ◽

Hla Class I ◽

Elite Controllers ◽

Myeloid Dendritic Cells ◽

Soluble Hla ◽

Antigen Presenting ◽

Hiv 1

ABSTRACT Dendritic cells represent a specialized class of professional antigen-presenting cells that are responsible for priming and maintaining antigen-specific effector cell responses and regulating immune activation by cytokine secretion. In HIV-1 infection, myeloid dendritic cells are highly dysfunctional, but mechanisms contributing to their functional alterations are not well defined. Here, we show that soluble molecules of the nonclassical major histocompatibility complex class Ib (MHC-Ib) antigen HLA-G are highly upregulated in the plasma during progressive HIV-1 infection, while levels of membrane-bound HLA-G surface expression on dendritic cells, monocytes, and T cells only slightly differ among HIV-1 progressors, HIV-1 elite controllers, and HIV-1-negative persons. These elevated levels of soluble HLA-G in progressive HIV-1 infection likely result from increased secretion of intracellularly stored HLA-G molecules in monocytes and dendritic cells and contribute to a functional disarray of dendritic cells by inhibiting their antigen-presenting properties, while simultaneously enhancing their secretion of proinflammatory cytokines. Interestingly, we observed that these immunoregulatory effects of soluble HLA-G were mainly mediated by interactions with the myelomonocytic HLA class I receptor leukocyte immunoglobulin-like receptor B2 (LILRB2; ILT4), while binding of soluble HLA-G to its alternative high-affinity receptor, LILRB1 (ILT2), appeared to be less relevant for its immunomodulatory functions on dendritic cells. Overall, these results demonstrate a critical role for soluble HLA-G in modulating the functional characteristics of professional antigen-presenting cells in progressive HIV-1 infection and suggest that soluble HLA-G might represent a possible target for immunotherapeutic interventions in HIV-1-infected persons.

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