A novel molecular interaction for the adhesion of follicular CD4 T cells to follicular DC

Abstract

Nectins and Nectin-like molecules (Necls) play a critical role in cell polarity within epithelia and in the nervous and reproductive systems. Recently, immune receptors specific for Nectins/Necls have been described. Since expression and distribution of Nectins/Necls is often subverted during tumorigenesis, it has been suggested that the immune system may use these receptors to recognize and eliminate tumors. Here we describe a novel immunoreceptor, WUCAM, which is expressed on human follicular B helper T cells (Tfh) and binds a Nectin/Necl family member, the poliovirus receptor (PVR), under both static and flow conditions. Futhermore, we demonstrate that PVR is abundantly expressed by follicular dendritic cells (FDC) within the germinal center. These results reveal a novel molecular interaction that mediates adhesion of Tfh to FDC and provide the first evidence that immune receptors for Nectins/Necls may be involved the generation of T cell-dependent antibody responses.

Recruitment of Grb2 and SHIP1 by the ITT-like motif of TIGIT suppresses granule polarization and cytotoxicity of NK cells

“…[10][11][12] TIGIT harbors one extracellular immunoglobulin domain, a type 1 transmembrane region, and an immunoglobulin tail tyrosine (ITT)-like phosphorylation motif followed by an ITIM (immunoreceptor tyrosine-based inhibition motif) of the cytoplasmic tail. 13 The physical ligands of TIGIT were identified as the poliovirus receptor (PVR, or CD155) and the PVRL2 (Nectin2, or CD112).…”

“…13 The physical ligands of TIGIT were identified as the poliovirus receptor (PVR, or CD155) and the PVRL2 (Nectin2, or CD112). 10,12 TIGIT can bind to PVR of human dendritic cells to enhance interleukin 10 (IL-10) production, which inhibits T-cell activation. 10 Kuchroo et al 14 showed that TIGIT harbors a T-cell-intrinsic inhibitory function to suppress T-cell activation.…”

A novel interface consisting of homologous immunoglobulin superfamily members with multiple functions

“…24 Washington University cell adhesion molecule Washington University cell adhesion molecule (WUCAM) is another recently identified novel receptor for PVR/CD155. 26 WUCAM sequences aligned with nectin-1-4, PVR/CD155, CD226 and CD96 in the distal Ig-V-type domain, according to the National Center Biotechnology Information cDNA database. WUCAM has a single Ig-V-type domain, a transmembrane-spanning sequence and a short cytoplasmic tail.…”

“…Furthermore, the interaction between WUCAM on human follicular B helper T cells and PVR/CD155 on follicular dendritic cell (DC) within the germinal center mediates adhesion of T follicular helper cells to follicular DCs and might facilitate the generation of T-cell-dependent antibody responses. 26 …”

Nectines et nectines-like

“…[11] exprimées à la surface de cellules adjacentes. Des membres de la famille des nectines et nectineslike sont aussi capables de former des interactions hétérophiliques en trans avec d'autres partenaires appartenant à la SFIg tels que DNAM1 (DNAX accessory molecule-1 ou CD226) [12], tactile (CD96) [13], CRTAM (Class I-restricted T cell-associated molecule) [14] et WUCAM (Washington University cell adhesion molecule) [15]. Ainsi, un réseau complexe de 17 trans-interactions hétérophiliques différentes avec les protéines nectines et nectines-like est actuellement décrit, certaines nectines étant associées à une fonction biologique (Figure 2).…”