背景 | CD300a, also known as LMIR1 (in rodents), CMRF-35H, IRp60, CLM-8, and MAIR-I, is a 60 kDa glycoprotein member of the immunoglobulin superfamily (1). Human CD300a consists of a 163 amino acid (aa) extracellular domain (ECD) with one Ig-like V-type domain, a 21 aa transmembrane segment, and a 98 aa cytoplasmic domain that contains three immunoreceptor tyrosine-based inhibitory motifs (ITIMs) and a non-canonical ITIM (2). Alternative splicing may generate additional isoforms that either lack the Ig-like domain or contain only the cytoplasmic domain. Within the ECD, human CD300a shares 40% and 43% aa sequence identity with mouse and rat LMIR1, respectively. In human, CD300a is expressed on peripheral blood eosinophils, mast cells, neutrophils, plasmacytoid dendritic cells, and various T cell subsets (3‑7). Antibody crosslinking of CD300a induces phosphorylation of tyrosine residues in the cytoplasmic domain. This leads to the recruitment of phosphatases SHIP, SHP-1, and SHP-2 and inhibition of NK cell, eosinophil, and mast cell activation (2, 3, 5‑7). Crosslinking of CD300a to other surface proteins such as SCF R or Fc epsilon RI on mast cells, Fc gamma RIIA on neutrophils, or CCR3 on mast cells and eosinophils inhibits downstream signaling from those receptors (5, 10‑12). CD300a crosslinking also limits the in vivo activities of these cells with a subsequent reduction of allergic inflammation symptoms (4, 11, 12). |
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