Disease relevance of CD300A

• Characterization of an antigen that is recognized on a melanoma showing partial HLA loss by CTL expressing an NK inhibitory receptor [1].
• The NK inhibitory receptor CD94/NKG2A was found on a significant proportion of CD8+ astrocytoma infiltrating lymphocytes [2].

High impact information on CD300A

• These findings demonstrate a novel pathway for suppressing the activity of human eosinophils, thus indicating IRp60 as a future potential target for the treatment of allergic and eosinophil-associated diseases [3].
• Furthermore, upon cross-linking, IRp60 underwent tyrosine phosphorylation and recruited SHP-1 but not SHP-2 [3].
• On NK cells, IRp60 cross-linking leads to the inhibition of cytotoxic activity vs target cells in vitro [4].
• IRp60 is constitutively expressed on mast cells but is down-regulated in vitro by the eosinophil proteins major basic protein and eosinophil-derived neurotoxin [4].
• The gene encoding for IREM-1 contains nine exons, is located on human chromosome 17 (17q25.1) and is homologous to previously identified molecules termed CMRF-35 and IRp60 [5].

Biological context of CD300A

• The CMRF-35H gene structure predicts for an independently expressed member of an ITIM/ITAM pair of molecules localized to human chromosome 17 [6].
• An immune complex-mediated cross-linking of IRp60 led to inhibition of IgE-induced degranulation and stem cell factor-mediated survival via a mechanism involving tyrosine phosphorylation, phosphatase recruitment, and termination of cellular calcium influx [4].
• The genes for the CMRF-35A and CMRF-35H molecules are closely linked on chromosome 17 [7].

Anatomical context of CD300A

• The function of these molecules is unknown, however the presence of putative immunoreceptor tyrosine-based inhibitory motifs (ITIM) in the cytoplasmic domain of the CMRF-35H molecule suggests that this molecule may play a regulatory role in leukocyte function [6].
• These data demonstrate a novel pathway for the regulation of human mast cell function and allergic responses, indicating IRp60 as a candidate target for future treatment of allergic and mast cell-associated diseases [4].
• Since IRp60 is also expressed by other cell types, including T cell subsets, monocytes and granulocytes, it may play a more general role in the negative regulation of different leukocyte populations [8].
• Specific radioreceptor assays for FSH and LH, which employ tissue receptors from rat testis and highly purified human FSH (LER 1575-C) and LH (Hartree IRC-2, 24/6/69) as standards, have been developed to determine the FSH-like and LH-like activities in pregnant mare serum gonadotropin (PMSG) [9].

Other interactions of CD300A

• This would further indicate that, like other ITIM/ITAM containing molecules, CMRF-35H/CMRF-35A will also play an important role in the immune response [6].
• Since there is a strong association between Ankylosing Spondylitis (AS) and HLA-B27, which is specifically recognized by the NK-inhibitory receptor KIR3DL1, this study evaluated the potential involvement of NK cells in AS [10].

Analytical, diagnostic and therapeutic context of CD300A

• Southern blot analysis revealed cross-hybridization with monkey and mouse genomic DNA, thus suggesting that IRp60 may be conserved among different species [8].
• Purified preparations of human luteinizing hormone (hLH), Hartree IRC-2, and NIH LER-960, have been examined after gel filtration of unlabelled and iodinated hormone [11].

References