Major Histocompatibility Complex Class II Molecule-Human Immunodeficiency Virus Peptide Analysis Using a Microarray Chip▿ †

Identification of major histocompatibility complex (MHC) class II binding peptides is a crucial step in rational vaccine design and immune monitoring. We designed a novel MHC class II molecule-peptide microarray binding assay and evaluated 346 peptides from already identified human immunodeficiency virus (HIV) epitopes and an additional set (n = 206) of 20-mer peptides, overlapping by 15 amino acid residues, from HIV type 1B (HIV-1B) gp160 and Nef as a paradigm. Peptides were attached via the N-terminal part to a linker that covalently binds to the epoxy glass slide. The 552 peptides were printed in triplicate on a single peptide microarray chip and tested for stable formation of MHC class II molecule-peptide complexes using recombinant soluble DRB1*0101(DR1), DRB1*1501(DR2), and DRB1*0401(DR4) molecules. Cluster analysis revealed unique patterns of peptide binding to all three, two, or a single MHC class II molecule. MHC class II binding peptides reside within previously described immunogenic regions of HIV gp160 and Nef, yet we could also identify new MHC class II binding peptides from gp160 and Nef. Peptide microarray chips allow the comprehensive and simultaneous screening of a high number of candidate peptide epitopes for MHC class II binding, guided by subsequent quality data extraction and binding pattern cluster analysis

The P2X4 purinergic receptor impacts liver regeneration after partial hepatectomy in mice through the regulation of biliary homeostasis

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NKp46 expression on NK cells as a prognostic and predictive biomarker for response to allo-SCT in patients with AML

International audienceNKp46 is a major determinant of natural killer (NK) cell function and it is implicated in tumor immune surveillance in acute myeloid leukemia (AML). The purpose of this study was to investigate the prognostic significance of NKp46 expression in an independent cohort of patients with AML, and to investigate the impact of NKp46 on clinical outcome after allogeneic stem cell transplantation (allo-SCT).NKp46 expression was assessed at diagnosis on NK cells by flow cytometry (N = 180 patients). Clinical outcome was evaluated with regard to NKp46 expression. Patients with NKp46high phenotype at diagnosis had better progression-free survival (PFS) and overall survival (OS) than patients with NKp46low phenotype (74.3% vs. 46.6%, p = 0.014; 82.6% vs. 57.1%, p = 0.010, respectively). In multivariate analysis, high NKp46 was an independent factor for improved OS (HR = 0.409, p = 0.010) and PFS (HR = 0.335, p = 0.011). Subgroup analysis revealed that allo-SCT had a favorable impact on PFS in patients with NKp46high phenotype (p = 0.025). By contrast, allo-SCT did not impact PFS in patients with low NKp46 expression (p = 0.303).In conclusion, we validate the prognostic value of NKp46 expression at diagnosis in AML. However, the prognostic value of NKp46 expression is limited to patients treated with allo-SCT, thus suggesting that NKp46 status may be predictive for allo-SCT responsiveness

Correction: NKp30 expression is a prognostic immune biomarker for stratification of patients with intermediate-risk acute myeloid leukemia

International audience[This corrects the article DOI: 10.18632/oncotarget.17747.]

NKp30 expression is a prognostic immune biomarker for stratification of patients with intermediate-risk acute myeloid leukemia

Cytogenetics and European Leukemia Net (ELN) genetic classification predict patients at increased risk of relapse in acute myeloid leukemia (AML) except in the intermediate risk group for which further prognostic determinants are required. We have previously shown that Natural Killer (NK) cell defects in AML are predictors of poor overall survival (OS). This study aimins at validating NKp30, a receptor that mediates NK activation, as a prognostic biomarker for AML patients with intermediate prognosis. NKp30 expression was prospectively assessed at diagnosis on NK cells from peripheral blood by flow cytometry (N = 201 patients). Clinical outcome was evaluated with regard to NKp30 status. In patients with intermediate cytogenetic (N = 162), NKp30(high) phenotype at diagnosis was predictive of better OS (HR = 0.26; 95% CI = [0.14-0.50]; P < 0.0001) and relapse-free survival (RFS) (HR = 0.21; 95% CI = [0.08-0.52]; P = 0.0007). In patients with intermediate ELN (N = 116), NKp30(high) phenotype at diagnosis was predictive of better OS (HR = 0.33; 95% CI = [0.16-0.67]; P = 0.0019) and RFS (HR = 0.24; 95% CI = [0.08-0.67]; P = 0.0058). In multivariate analysis, high NKp30 expression independently predicted improved OS (HR = 0.56, P = 0.046) and RFS (HR = 0.37, P = 0.048). Consistently, cumulative incidence of relapse (CIR) was lower in patients with high NKp30 expression (HR = 0.37, P = 0.026). In conclusion, we propose NKp30 status as a simple and early prognostic biomarker that identifies intermediate-risk patients with poor prognosis who otherwise may not be identified with existing risk stratification systems

The MICADO first-light imager for the ELT: first steps of the SCAO system MAIT

International audienceMICADO is the ELT first light instrument, an imager working at the diffraction limit of the telescope thanks to two adaptive optics (AO) modes: a single conjugate one (SCAO), available at the instrument first light and developed by the MICADO consortium, and a multi conjugate one (MCAO), developed by the MORFEO consortium. Although the project final design review process is about to be completed, the review board and ESO acknowledged that "the review of the final design can be considered complete for the majority of the MICADO sub-systems" and agreed that MICADO can start manufacturing. For the MICADO SCAO module, we have started the manufacturing of several parts: the majority of the SCAO optics and of the SCAO mechanics, the real-time computer software and the instrument control software. This manufacturing is ordered in several steps to allow the progressive integration of a first full AO close loop with the final SCAO parts. In this contribution, we will focus on the first two steps: on our AO Sésame bench and the so-called "&beta; flat configuration". We will present the status of this manufacturing and the first results obtained

MICADO SCAO: to be or not to be... in MAIT

International audienceMICADO SCAO: to be or not to be... in MAI

The MICADO first-light imager for the ELT: first steps of the SCAO system MAIT

International audienceMICADO is the ELT first light instrument, an imager working at the diffraction limit of the telescope thanks to two adaptive optics (AO) modes: a single conjugate one (SCAO), available at the instrument first light and developed by the MICADO consortium, and a multi conjugate one (MCAO), developed by the MORFEO consortium. Although the project final design review process is about to be completed, the review board and ESO acknowledged that "the review of the final design can be considered complete for the majority of the MICADO sub-systems" and agreed that MICADO can start manufacturing. For the MICADO SCAO module, we have started the manufacturing of several parts: the majority of the SCAO optics and of the SCAO mechanics, the real-time computer software and the instrument control software. This manufacturing is ordered in several steps to allow the progressive integration of a first full AO close loop with the final SCAO parts. In this contribution, we will focus on the first two steps: on our AO Sésame bench and the so-called "&beta; flat configuration". We will present the status of this manufacturing and the first results obtained

MICADO SCAO: to be or not to be... in MAIT

International audienceMICADO SCAO: to be or not to be... in MAI