Effect of Specific Mutations in Cd300 Complexes Formation; Potential Implication of Cd300f in Multiple Sclerosis

Abstract

Herein, we have used bioinformatics tools to predict five clusters defining ligand-binding sites on the extracellular domain of human CD300b receptor, presumably involved in the formation of both homodimers and heterodimers with other CD300 family members. Site-directed mutagenesis revealed residues glutamic acid 28 and glutamine 29 in cluster 5 to be necessary for the formation of CD300b complexes. Surprisingly, the disruption of cluster 2 and 4 reconstituted the binding capability lost by the mutation of residues glutamic acid 28 to alanine, glutamine 29 to alanine (E28A-Q29G). We identified a missense mutation arginine 33 to glutamine (R33Q) in CD300f by direct sequencing of exon 2 in peripheral blood samples from 50 patients with multiple sclerosis (MS). Levels of expression of CD300f were almost undetectable on monocytes from the patient bearing the R33Q mutation compared with healthy individuals. Whereas R33Q mutation had no effect in the formation of CD300f complexes, the inhibition of protein synthesis with cycloheximide indicated that CD300f R33Q is less stable than native CD300f. Finally, we report that the levels of expression of CD300f on the surface of classical and intermediate monocytes from MS patients are significantly lower when compared to the same cell populations in healthy individuals.

CD300 family receptors regulate eosinophil survival, chemotaxis, and effector functions

“…Interestingly, CD300 family of receptors can interact with each other to form homo and heterodimers. For example, human CD300b acts as a modifier of CD300c signaling and CD300c is capable of interacting with other CD300 family receptors including CD300a, CD300f, and CD300e but no other Ig‐superfamily receptors . Thus, in addition to their diversity in ligand recognition, CD300 family receptors may elicit different signaling strengths dependent on the expression of additional CD300 family members.…”

Inhibitory Receptors and Checkpoints in Human NK Cells, Implications for the Immunotherapy of Cancer

“…IRp60/CD300a is an inhibitory receptor belonging to CD300 family, a set of genes clustered on chromosome 17 coding for receptors, predominantly expressed on leukocytes, able to generate inhibitory and activating signals regulating different immune processes, such as phagocytosis, cytokine release, proliferation and diseases (80,(106)(107)(108)(109)(110)(111)(112). In addition to NK cells, IRp60 is broadly expressed in cells of myeloid or lymphoid origin such as neutrophils (113), eosinophils (106), mast cells (114), pDC (113), B and T cells (115).…”

CD300 receptor family in viral infections

“…Over the past few years, several publications have highlighted the important role the CD300 family of receptors has in complex biological processes such as phagocytosis, proliferation, and cytokine production [7, 12,13,17,24,25,30,31,39,40], and in a variety of diseases, including autoimmune disorders, allergic and inflammatory diseases, hematological malignancies, sepsis, etc. [7,12,17,19,21,33,[41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58]. Here, we review several aspects involving the CD300 molecules and viral infections, including how viruses use these receptors to interact with and enter cells or to escape from the attack of the immune system.…”

“…Furthermore, mouse CD300f has also been demonstrated to bind the ITAM‐containing adaptor FcRγ chain (Figure ) . An additional layer of complexity related to both the expression and signaling pathways of this receptor family is that their members can interact with each other to form homo and heterodimers, which is dependent on their immunoglobulin domains . Furthermore, it has been described that CD300b also has the ability to form a complex with toll‐like receptor 4 (TLR4), and therefore regulates LPS‐induced responses on myeloid cells , while mouse CD300f associates with IL‐4 receptor α and amplifies IL‐4‐induced immune cell responses (Figure ).…”