CD40 ligand dictated signaling bias
T cells are pivotal for innate and adaptive immune response. On, T cell a co-stimulatory molecule CD40 ligand is present that binds to the CD40 receptor. CD40L a type II membrane protein, consists of 261 amino acids belong to a member of the TNF-family. There are 193 amino acids present at the extra...
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2020-01-01
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| Series: | BLDE University Journal of Health Sciences |
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| Online Access: | http://www.bldeujournalhs.in/article.asp?issn=2468-838X;year=2020;volume=5;issue=3;spage=27;epage=27;aulast=Bammigatti;type=0 |
| Summary: | T cells are pivotal for innate and adaptive immune response. On, T cell a co-stimulatory molecule CD40 ligand is present that binds to the CD40 receptor. CD40L a type II membrane protein, consists of 261 amino acids belong to a member of the TNF-family. There are 193 amino acids present at the extracellular domain of CD40 ligand requires basic amino acid residue K143, R203, R207 for receptor binding, however, the CD40 molecule requires acidic amino acid residue D84, E114, E117 for activation of the different signaling cascade. Binding of CD40L with CD40 receptors activate JAK-STAT signaling, inflammatory cytokines, chemokines along with various downstream transcription factor molecules. As it is well studied, deficiency in CD40 ligand leads to an autoimmune disorder called Hyper X-linked IgM syndrome. So studies on HXIM syndrome revealed that an extracellular domain of CD40 ligand is cardinal for receptor binding. Depending on binding strength, signaling skew will be decided. Stronger will activate p38 MAPK (anti-parasitic in nature) by inducing IL-12 however, weaker will activate ERK-1/2 (pro-parasitic in nature) by inducing IL-10. The specific binding of the receptor is necessary to decode the message encoded by binding stimulation. Therefore, CD40 ligand wild type residues bind with CD40 site-directed mutagenized with different amino acids. These mutant CD40 ligands upon binding with CD40 reveal a better insight into the nature of host-pathogen interaction, inflammatory cytokines, chemokines and signaling molecules. Therefore, we can assume CD40 ligand mutants have a role in anti-leishmanial function. |
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| ISSN: | 2468-838X 2456-1975 |