Abstracts (complete list) - Wissenschaft Online

Viet Bui, Andreas Diefenbach
Molecular cloning and functional characterization of a novel
stimulatory immunoreceptor expressed by myeloid cells
Innate immune cells express stimulatory receptors to recognize diseased cells or
pathogens. We have identified and cloned a novel stimulatory immunoreceptor
expressed in mice. This novel receptor contains a single Ig-V domain and is a member
of the Ig-superfamily. A charged residue in the transmembrane domain indicated
association with a signaling adaptor molecule. Indeed, the receptor could not be
expressed in cell lines lacking signaling adaptor molecules. Our studies demonstrated a
requirement of the signaling adapter KARAP/DAP12 for surface expression and
signaling. We have generated a monoclonal antibody specific for this receptor.
Preliminary experiments revealed the receptor to be expressed by myeloid cells such as
dendritic cells, macrophages, and neutrophils while being absent from T, B, NK, and
NKT cells. Interestingly, we identified another gene within the same locus encoding
another immune receptor sharing 87% identity in the extracellular domain. These data
suggest that both receptors may recognize the same cognate ligand. In contrast to the
stimulatory receptor, this second receptor possesses a consensus ITIM motif in its
cytoplasmic tail region suggesting it to be an inhibitory receptor. This inhibitory receptor
shares the same expression pattern as the stimulatory receptor. Whereas stimulation of
myeloid cells leads to the down-regulation of the stimulatory receptor, its inhibitory
counterpart seems to be up-regulated. Based on these initial findings, we hypothesize
that these two receptors are paired stimulatory/inhibitory receptors expressed by
myeloid cells that likely recognize the same cognate antigen. The inverse nature of their
expression would suggest that this receptor pair is an important molecular switch
regulating the function of myeloid cells.