KIR-HLA intercourse in HIV disease

CMV infection represents a major complication in hematopoietic stem cell transplantation, which compromises graft outcome. Downregulation of HLA class I expression is one mechanism by which CMV evades T cell–mediated immune detection, rendering infected cells vulnerable to killer cell Ig-like receptor (KIR)+ NK cells. In this study, we observed that the amplified NKG2C+ NK cell population observed specifically in CMV seropositive individuals mainly expressed KIR2DL receptors. We have shown that HLA class I expression was downregulated on CMV-infected immature dendritic cells (iDCs), which escape to HLA-A2-pp65–specific T lymphocytes but strongly trigger the degranulation of KIR2D+ NK cells. CMV infection conferred a vulnerability of C2C2+ iDCs to educated KIR2DL1+ and KIR2DL3+ NK cell subsets. Alloreactivity of KIR2DL1+ NK cell subsets against C1C1+ iDCs was maintained independently of CMV infection. Unexpectedly, CMV-infected C1C1+ iDCs did not activate KIR2DL3+ NK cell reactivity, suggesting a potential CMV evasion to KIR2DL3 NK cell recognition. Altogether, the coexpression of KIR and NKG2C on expanded NK cell subsets could be related to a functional contribution of KIR in CMV infection and should be investigated in hematopoietic stem cell transplantation, in which the beneficial impact of CMV infection has been reported on the graft-versus-leukemia effect.

Section: Discussionsupporting

confidence: 61%

Amplified NKG2C+ NK Cells in Cytomegalovirus (CMV) Infection Preferentially Express Killer Cell Ig-like Receptor 2DL: Functional Impact in Controlling CMV-Infected Dendritic Cells

Djaoud

David

Bressollette

et al. 2013

“…The recent interest in KIR3DS1 can be explained, not only by the newly discovered possibility to detect its expression by flow cytometry (30 -33) but also by the genetic associations favoring protection to AIDS (27)(28)(29)(42)(43)(44), clearance of hepatitis C virus (23) and resistance to cervical neoplasia (25,26) or hepatocellular carninoma (24). In this study, we show for the first time that, even for individuals with a very low proportion of KIR3DS1 ϩ NK cells on resting PBMCs, the expression of KIR3DS1 is induced on NK cells after stimulation with stimulator cells (221, K562, EBV-B cell lines, and B cells), poly(IC), and cytokines as IL-15 and IL-2.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, HLA-Bw4 tetramers loaded with various peptides did not succeed in binding to KIR3DS1 (22). This absence of interaction in vitro does not exclude protection by the KIR3DS1-Bw4 association as suggested by genetic studies for the acute hepatitis C virus (23,24), the human papillomavirus (25,26), and HIV-1 infections (27)(28)(29). The recent findings showing that KIR3DS1 is actually expressed on the cell surface and is detectable by flow cytometry with the KIR3DL1/S1-specific mAb, Z27, at a very low intensity of fluorescence (30 -33), led to study KIR3DS1 expression and to investigate a potential interaction between KIR3DS1 and HLA-Bw4.…”

mentioning

confidence: 91%

Phenotypic and Functional Analyses of KIR3DL1+ and KIR3DS1+ NK Cell Subsets Demonstrate Differential Regulation by Bw4 Molecules and Induced KIR3DS1 Expression on Stimulated NK Cells

Morvan

Willem

Gagne

et al. 2009

Recently, the Z27 mAb was shown to recognize the NK cell-activating receptor KIR3DS1, and several genetic studies suggest that the most probable ligands of KIR3DS1 are HLA class I molecules with the Bw4 motif. Despite these findings, the attempts to establish a functional interaction between KIR3DS1 and its potential ligand have been unsuccessful. Here, we study the proliferation and cytotoxicity of KIR3DS1

“…Their binding may be influenced also by peptide bound to class I (25)(26)(27)(28)(29)(30). KIR variation, in conjunction with that in HLA class I, is associated with diseases, including viral infections (31,32), autoimmunity (33,34), and complications of pregnancy (35). The broad specificity of LILRB1 and LILRB2 results from their interaction with the conserved b 2 -microglobulin (b 2 m) subunit (LILRB1) and/or the a3 domain of HLA class I (20,36).…”

mentioning

confidence: 99%

HLA Class I Allelic Sequence and Conformation Regulate Leukocyte Ig-Like Receptor Binding

Jones

Kosmoliaptsis

Apps

et al. 2011

110

143

Leukocyte Ig-like receptors (LILRs) are a family of innate immune receptors predominantly expressed by myeloid cells that can alter the Ag presentation properties of macrophages and dendritic cells. Several LILRs bind HLA class I. Altered LILR recognition due to HLA allelic variation could be a contributing factor in disease. We comprehensively assessed LILR binding to >90 HLA class I alleles. The inhibitory receptors LILRB1 and LILRB2 varied in their level of binding to different HLA alleles, correlating in some cases with specific amino acid motifs. LILRB2 displayed the weakest binding to HLA-B*2705, an allele genetically associated with several autoimmune conditions and delayed progression of HIV infection. We also assessed the effect of HLA class I conformation on LILR binding. LILRB1 exclusively bound folded β2-microglobulin–associated class I, whereas LILRB2 bound both folded and free H chain forms. In contrast, the activating receptor LILRA1 and the soluble LILRA3 protein displayed a preference for binding to HLA-C free H chain. To our knowledge, this is the first study to identify the ligand of LILRA3. These findings support the hypothesis that LILR-mediated detection of unfolded versus folded MHC modulates immune responses during infection or inflammation.