Anti-CD6 monoclonal antibody, clone 7C0

Dendritic Cells (DC) are natural adjuvants able to elicit specific cellular interactions and priming of naive T cells at a mature stage of their differentiation. Recent genomic approaches helped defining DC or Langherans Cells (LC) in more molecular terms. DC-SIGN, the DC specific ICAM-3 grabbing non integrin is a C-type lectin, absent on LC but expressed on dermal, lymph node and tonsils DC. DC-SIGN is defined as an ICAM-3 receptor supporting DC mediated-T cell proliferation. Moreover, DC-SIGN plays an important role in binding and presentation of HIV virions, because DC-SIGN specifically binds the gp120 coat protein of HIV.DC-SIGN also plays a part in DC trafficking since it not only binds ICAM-3 but also ICAM-2 expressed by many endothelial cells, supporting tethering and rolling of DC on endothelium and chemokine induced-transmigration of DC across both resting and activated endothelium in vitro. ALCAM (Activated Leukocyte Cell Adhesion Molecule) is another cell surface protein expressed by DC upon differentiation from monocytes. ALCAM appears to be expressed on activated leukocytes and might be involved in inflammatory processes. ALCAM belongs to the IgG superfamily of proteins and mediate heterotypic (T cell antigen ligand CD6) or homotypic interactions. ALCAM is linked to the cytoskeleton and might play a role in DC migration. Measurements of cell/cell contacts at single molecular levels using optical traps is a useful tool to investigate intercellular interactions. (C) 2002 Editions scientifiques et medicales Elsevier SAS. All rights reserved.

Objectives: To investigate the roles of 2 polymorphisms of the tumor necrosis factor (TNF) receptor superfamily member 1A (TNFRSF1A) gene, rs1800693 (a common variant) and rs4149584 (a coding polymorphism that results in an amino acid substitution-R92Q), as genetic modifiers of multiple sclerosis (MS), and to evaluate their potential functional implications in the disease. Methods: The effects of rs1800693 and rs4149584 on 2 measures of disease severity, age at disease onset and Multiple Sclerosis Severity Score, were analyzed in 2,032 patients with MS. In a subgroup of patients, serum levels of the soluble form of TNF-R1 (sTNF-R1) were measured by ELISA; mRNA expression levels of the full-length TNF-R1 and Delta 6-TNF-R1 isoform were investigated in peripheral blood mononuclear cells (PBMC) by real-time PCR; cell surface expression of the TNF-R1 was determined in T cells by flow cytometry. Results: For rs4149584, R92Q carriers were younger at disease onset and progressed slower compared to noncarriers. However, no association with disease severity was observed for rs1800693. Serum levels of sTNF-R1 and mRNA expression levels of the full-length receptor were significantly increased in patients with MS carrying the R92Q mutation (p = 0.003 and p = 0.011, respectively), but similarly distributed among rs1800693 genotypes; cell surface TNF-R1 expression in T cells did not differ between rs4149584 and rs1800693 genotypes. The truncated soluble Delta 6-TNF-R1 isoform was identified in PBMC from patients carrying the risk allele for rs1800693. Conclusions: These findings suggest that both rs1800693 and rs4149584 TNFRSF1A polymorphisms have functional consequences in the TNF-R1.