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Differential but competitive binding of Nogo protein and class i major histocompatibility complex (MHCI) to the PIR-B ectodomain provides an inhibition of cells.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2011 Jul 22; Vol. 286 (29), pp. 25739-47. Date of Electronic Publication: 2011 Jun 02. - Publication Year :
- 2011
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Abstract
- Binding of class I MHC molecules (MHCI) to an inhibitory receptor, PIR-B, expressed on B cells and myeloid cells provides constitutive cellular inhibition, thus ensuring peripheral tolerance. Recent unexpected findings pointed to a novel inhibitory role of PIR-B in neurite regeneration through binding to three axonal outgrowth inhibitors of myelin, including Nogo. Thus, it becomes interesting to determine whether the actions of the inhibitory myelin proteins and MHCI could coexist independently or be mutually exclusive as to the PIR-B-mediated immune and neural cell inhibition. Here, we present data supporting the competition of Nogo- and MHCI-mediated inhibition where they coexist. Kinetic analyses of Nogo and MHCI binding to the whole or a part of the recombinant PIR-B ectodomain revealed that PIR-B binds with higher affinity to Nogo than MHCI and that the MHCI binding only occurred with the N-terminal domains of PIR-B, whereas Nogo binding occurred with either the N- or C-terminal ectodomains. Importantly, kinetic tests indicated that the binding to PIR-B of Nogo and MHCI was competitive. Both endogenous and exogenous Nogo intensified the PIR-B-mediated suppression of interleukin-6 release from lipopolysaccharide-stimulated wild-type, but not PIR-B-deficient, cultured mast cells, indicating that PIR-B mediates Nogo-induced inhibition. Thus, we propose a novel mechanism by which PIR-B-mediated regulation is achieved differentially but competitively via MHCI and Nogo in cells of the immune system.
- Subjects :
- Animals
Female
HLA Antigens metabolism
HLA-G Antigens
Humans
Immunologic Factors metabolism
Interleukin-6 metabolism
Lipopolysaccharides pharmacology
Mast Cells drug effects
Mice
Mice, Inbred C57BL
Myelin-Associated Glycoprotein metabolism
Neurotransmitter Agents metabolism
Nogo Proteins
Protein Structure, Tertiary
Rats
Substrate Specificity
beta 2-Microglobulin metabolism
Binding, Competitive
Histocompatibility Antigens Class I metabolism
Mast Cells metabolism
Myelin Proteins metabolism
Receptors, Immunologic chemistry
Receptors, Immunologic metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1083-351X
- Volume :
- 286
- Issue :
- 29
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 21636572
- Full Text :
- https://doi.org/10.1074/jbc.M110.157859