Identification and Characterization of CD300H, a New Member of the Human CD300 Immunoreceptor Family

J Biol Chem. 2015 Sep 4;290(36):22298-308. doi: 10.1074/jbc.M115.643361. Epub 2015 Jul 28.

Abstract

Recruitment of circulating monocytes and neutrophils to infection sites is essential for host defense against infections. Here, we identified a previously unannotated gene that encodes an immunoglobulin-like receptor, designated CD300H, which is located in the CD300 gene cluster. CD300H has a short cytoplasmic tail and associates with the signaling adaptor proteins, DAP12 and DAP10. CD300H is expressed on CD16(+) monocytes and myeloid dendritic cells. Ligation of CD300H on CD16(+) monocytes and myeloid dendritic cells with anti-CD300H monoclonal antibody induced the production of neutrophil chemoattractants. Interestingly, CD300H expression varied among healthy subjects, who could be classified into two groups according to "positive" and "negative" expression. Genomic sequence analysis revealed a single-nucleotide substitution (rs905709 (G → A)) at a splice donor site on intron 1 on either one or both alleles. The International HapMap Project database has demonstrated that homozygosity for the A allele of single nucleotide polymorphism (SNP) rs905709 ("negative" expression) is highly frequent in Han Chinese in Beijing, Japanese in Tokyo, and Europeans (A/A genotype frequencies 0.349, 0.167, and 0.138, respectively) but extremely rare in Sub-Saharan African populations. Together, these results suggest that CD300H may play an important role in innate immunity, at least in populations that carry the G/G or G/A genotype of CD300H.

Keywords: chemokine; dendritic cell; monocyte; neutrophil; single-nucleotide polymorphism (SNP).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Asian People / genetics
  • Cell Line, Tumor
  • Cells, Cultured
  • Cytokines / genetics
  • Cytokines / immunology
  • Cytokines / metabolism
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Gene Frequency
  • Genotype
  • HEK293 Cells
  • Humans
  • Immunity, Innate / genetics
  • Immunity, Innate / immunology*
  • Immunoblotting
  • Mice
  • Molecular Sequence Data
  • Multigene Family*
  • Neutrophils / immunology
  • Neutrophils / metabolism
  • Phylogeny
  • Polymorphism, Single Nucleotide / genetics
  • Polymorphism, Single Nucleotide / immunology
  • Protein Isoforms / genetics
  • Protein Isoforms / immunology
  • Protein Isoforms / metabolism
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / immunology*
  • Receptors, Immunologic / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Amino Acid
  • U937 Cells
  • White People / genetics

Substances

  • CD300H protein, human
  • Cytokines
  • Protein Isoforms
  • Receptors, Immunologic

Associated data

  • GENBANK/LC013475
  • GENBANK/LC013476