Robert F. Dubose

A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function

Dendritic cells are rare haematopoietic cells that reside in a number of organs and tissues. By capturing, processing and presenting antigens to T cells, dendritic cells are essential for immune surveillance and the regulation of specific immunity. Several members of the tumour necrosis factor receptor (TNFR) superfamily are integral to the regulation of the immune response. These structurally related proteins modulate cellular functions ranging from proliferation and differentiation to inflammation and cell survival or death. The functional activity of dendritic cells is greatly increased by signalling through the TNFR family member CD40 (refs 7, 8). Here we report the characterization of RANK (for receptor activator of NF-κB), a new member of the TNFR family derived from dendritic cells, and the isolation of a RANK ligand (RANKL) by direct expression screening. RANKL augments the ability of dendritic cells to stimulate naive T-cell proliferation in a mixed lymphocyte reaction, and increases the survival of RANK+T cells generated with interleukin-4 and transforming growth factor (TGF)-β. Thus RANK and RANKL seem to be important regulators of interactions between T cells and dendritic cells.

The identification of seven metalloproteinase-disintegrin (ADAM) genes from genomic libraries

Metalloproteinase-disintegrins (ADAMs) are membrane-spanning multi-domain proteins containing a zinc metalloproteinase domain and a disintegrin domain which may serve as an integrin ligand. Based on a conserved sequence within the disintegrin domain, GE(E/Q)CDCG, seven genes were isolated from a human genomic library. Two of these genes lack introns and show testis-specific expression (ADAM20 and ADAM21), while the other two genes contain introns (ADAM22 and ADAM23) and are expressed predominantly in the brain. In addition, three pseudogenes were isolated; one of which evolved from ADAM21. Human chromosomal mapping indicated that ADAM22 and ADAM23 mapped to chromosome 7q21 and 2q33, respectively, while the three pseudogenes 1-2, 3-3, and 1-32 mapped to chromosome 14q24.1, 8p23, and 14q24.1, respectively. An ancestral analysis of all known ADAMs indicates that the zinc-binding motif in the catalytic domain arose once in a common ancestor and was lost by those members lacking this motif.