Nectin-like Protein 2 Defines a Subset of T-cell Zone Dendritic Cells and Is a Ligand for Class-I-restricted T-cell-associated Molecule

Abstract

Dendritic cells (DCs) are a phenotypically and functionally heterogenous population of leukocytes with distinct subsets serving a different set of specialized immune functions. Here we applied an in vitro whole cell panning approach using antibody phage display technology to identify cell-surface epitopes specifically expressed on human blood BDCA3 ؉ DCs. A single-chain antibody fragment (anti-1F12 scFv) was isolated that recognizes a conserved surface antigen expressed on both human BDCA3 ؉ DCs and mouse CD8␣ ؉ DCs. We demonstrate that anti-1F12 scFv binds Nectin-like protein 2 (Necl2, Tslc1, SynCaM, SgIGSF, or Igsf4), an adhesion molecule involved in tumor suppression, synapse formation, and spermatogenesis. Thus, Necl2 defines a specialized subset of DCs in both mouse and human. We further show that Necl2 binds Class-I-restricted T-cellassociated molecule (CRTAM), a receptor primarily expressed on activated cytotoxic lymphocytes. When present on antigen presenting cells, Necl2 regulates IL-22 expression by activated CD8 ؉ T-cells. We propose that Necl2/CRTAM molecular pair could regulate a large panel of cell/cell interactions both within and outside of the immune system.

Clinical significance of CADM1/TSLC1/IgSF4 expression in adult T-cell leukemia/lymphoma

“…The CADM1-positive cells in reactive lymph node possibly correspond to histiocytes, including dendritic cells because a subset of T-cell zone dendritic cells was reported to express CADM1 (Necl-2) within the lymph node. 24,25 We examined 90 tissue samples from patients with various types of lymphoma, including 36 patients with ATLL and 54 with non-ATLL lymphomas, using erythrocytes and nerve fascicles as positive controls. Of the non-ATLL samples, 29 cases were T-or NK-cell lymphomas, 37 cases were B-cell lymphomas and 2 cases were null-cell lymphomas.…”

The equivalents of human blood and spleen dendritic cell subtypes can be generated in vitro from human CD34+ stem cells in the presence of fms-like tyrosine kinase 3 ligand and thrombopoietin

“…Nonetheless, CLEC9A and XCR1 represent two molecules that are unique to the CD141 1 DCs in human blood and can thus also be used to distinguish this subset. [16][17][18]20,21 The CD1b/c 1 DC population represented the largest population among the cultured DCs and the CLEC9A 1 DCs the smallest. Like the blood, there were a large number of HLA-DR 1 Lineage 2 cells that Human DC subtypes generated in vitro AI Proietto et al 452 did not express a DC marker (the DC marker-negative population).…”

“…14 The CD141 1 DCs have been suggested to be equivalent to the mouse CD8 1 DCs sharing a similar transcriptional signature 15 and expression of Necl2, CLEC9A and XCR1. [16][17][18][19][20][21] Furthermore, the CD141 1 DCs have been shown to produce IL-12p70 and cross-present antigen, [20][21][22][23] both characteristics of the mouse CD8 1 DC subset. The CD1b/c 1 DC is thought to be the equivalent of the mouse CD8 2 DC, based on a similar transcriptional profile.…”

From skin dendritic cells to a simplified classification of human and mouse dendritic cell subsets

“…Based on the transcriptomic [33], functional [30,34] and developmental [35] [31,33]. Both subsets selectively express the membrane markers CADM1 [36], CLEC9A [37][38][39] and XCR1 [33,40,41] but are negative for SIRPa. Interestingly, XCL1, the chemokine ligand for XCR1 is selectively expressed by both activated NK and CD8 1 T cells [42] and Xcl1 mRNA is stored in central memory CD8 1 T lymphocytes [41].…”