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Residue-Specific Message Encoding in CD40-Ligand

CD40-Ligand (CD40L)-CD40 interaction regulates immune responses against pathogens, autoantigens, and tumor and transplantation antigens. Single amino acid mutations within the 115–155 amino acids stretch, which is responsible for CD40L functions, result in XIgM syndrome. We hypothesize that each of...

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Autores principales: Sarode, Aditya Yashwant, Jha, Mukesh Kumar, Zutshi, Shubhranshu, Ghosh, Soumya Kanti, Mahor, Hima, Sarma, Uddipan, Saha, Bhaskar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7452233/
https://www.ncbi.nlm.nih.gov/pubmed/32827854
http://dx.doi.org/10.1016/j.isci.2020.101441
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author Sarode, Aditya Yashwant
Jha, Mukesh Kumar
Zutshi, Shubhranshu
Ghosh, Soumya Kanti
Mahor, Hima
Sarma, Uddipan
Saha, Bhaskar
author_facet Sarode, Aditya Yashwant
Jha, Mukesh Kumar
Zutshi, Shubhranshu
Ghosh, Soumya Kanti
Mahor, Hima
Sarma, Uddipan
Saha, Bhaskar
author_sort Sarode, Aditya Yashwant
collection PubMed
description CD40-Ligand (CD40L)-CD40 interaction regulates immune responses against pathogens, autoantigens, and tumor and transplantation antigens. Single amino acid mutations within the 115–155 amino acids stretch, which is responsible for CD40L functions, result in XIgM syndrome. We hypothesize that each of these amino acids of CD40L encodes specific message that, when decoded by CD40 signaling, induces a specific profile of functions. We observed that every single substitution in the XIgM-related amino acids in the 115–155 41-mer peptide in CD40L selectively altered CD40 signaling and effector functions—cytokine productions, HMGCoA reductase, ceramide synthase, inducible nitric oxide synthase and arginase expression, survival of B cells, and control of Leishmania infection and anti-leishmanial T cell response—suggesting residue-specific encoding of a distinct set of messages that collectively define CD40L pleiotropy, serve as a target for engineering the ligand to generate superagonists as immunotherapeutic, and implicate the evolutionary diversification of functions among the ligands in a protein superfamily.
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spelling pubmed-74522332020-08-31 Residue-Specific Message Encoding in CD40-Ligand Sarode, Aditya Yashwant Jha, Mukesh Kumar Zutshi, Shubhranshu Ghosh, Soumya Kanti Mahor, Hima Sarma, Uddipan Saha, Bhaskar iScience Article CD40-Ligand (CD40L)-CD40 interaction regulates immune responses against pathogens, autoantigens, and tumor and transplantation antigens. Single amino acid mutations within the 115–155 amino acids stretch, which is responsible for CD40L functions, result in XIgM syndrome. We hypothesize that each of these amino acids of CD40L encodes specific message that, when decoded by CD40 signaling, induces a specific profile of functions. We observed that every single substitution in the XIgM-related amino acids in the 115–155 41-mer peptide in CD40L selectively altered CD40 signaling and effector functions—cytokine productions, HMGCoA reductase, ceramide synthase, inducible nitric oxide synthase and arginase expression, survival of B cells, and control of Leishmania infection and anti-leishmanial T cell response—suggesting residue-specific encoding of a distinct set of messages that collectively define CD40L pleiotropy, serve as a target for engineering the ligand to generate superagonists as immunotherapeutic, and implicate the evolutionary diversification of functions among the ligands in a protein superfamily. Elsevier 2020-08-06 /pmc/articles/PMC7452233/ /pubmed/32827854 http://dx.doi.org/10.1016/j.isci.2020.101441 Text en © 2020 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Sarode, Aditya Yashwant
Jha, Mukesh Kumar
Zutshi, Shubhranshu
Ghosh, Soumya Kanti
Mahor, Hima
Sarma, Uddipan
Saha, Bhaskar
Residue-Specific Message Encoding in CD40-Ligand
title Residue-Specific Message Encoding in CD40-Ligand
title_full Residue-Specific Message Encoding in CD40-Ligand
title_fullStr Residue-Specific Message Encoding in CD40-Ligand
title_full_unstemmed Residue-Specific Message Encoding in CD40-Ligand
title_short Residue-Specific Message Encoding in CD40-Ligand
title_sort residue-specific message encoding in cd40-ligand
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7452233/
https://www.ncbi.nlm.nih.gov/pubmed/32827854
http://dx.doi.org/10.1016/j.isci.2020.101441
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