Residue-Specific Message Encoding in CD40-Ligand
Summary: 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...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-09-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004220306337 |
| _version_ | 1819055291402027008 |
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| author | Aditya Yashwant Sarode Mukesh Kumar Jha Shubhranshu Zutshi Soumya Kanti Ghosh Hima Mahor Uddipan Sarma Bhaskar Saha |
| author_facet | Aditya Yashwant Sarode Mukesh Kumar Jha Shubhranshu Zutshi Soumya Kanti Ghosh Hima Mahor Uddipan Sarma Bhaskar Saha |
| author_sort | Aditya Yashwant Sarode |
| collection | DOAJ |
| description | Summary: 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. |
| first_indexed | 2024-12-21T13:05:11Z |
| format | Article |
| id | doaj.art-ac699dd6b19e4bdaa23c6063e0869fe8 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-21T13:05:11Z |
| publishDate | 2020-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-ac699dd6b19e4bdaa23c6063e0869fe82022-12-21T19:03:03ZengElsevieriScience2589-00422020-09-01239101441Residue-Specific Message Encoding in CD40-LigandAditya Yashwant Sarode0Mukesh Kumar Jha1Shubhranshu Zutshi2Soumya Kanti Ghosh3Hima Mahor4Uddipan Sarma5Bhaskar Saha6National Centre for Cell Science, Lab-5, Pathogenesis and Cellular Response, Ganeshkhind, Pune, Maharashtra 411007, India; Corresponding authorNational Centre for Cell Science, Lab-5, Pathogenesis and Cellular Response, Ganeshkhind, Pune, Maharashtra 411007, IndiaNational Centre for Cell Science, Lab-5, Pathogenesis and Cellular Response, Ganeshkhind, Pune, Maharashtra 411007, IndiaNational Centre for Cell Science, Lab-5, Pathogenesis and Cellular Response, Ganeshkhind, Pune, Maharashtra 411007, IndiaNational Centre for Cell Science, Lab-5, Pathogenesis and Cellular Response, Ganeshkhind, Pune, Maharashtra 411007, IndiaNational Centre for Cell Science, Lab-5, Pathogenesis and Cellular Response, Ganeshkhind, Pune, Maharashtra 411007, IndiaNational Centre for Cell Science, Lab-5, Pathogenesis and Cellular Response, Ganeshkhind, Pune, Maharashtra 411007, India; Trident Academy of Creative Technology, Bhubaneswar, Orissa 751024, India; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004220306337Biochemical MechanismBiochemistryImmunology |
| spellingShingle | Aditya Yashwant Sarode Mukesh Kumar Jha Shubhranshu Zutshi Soumya Kanti Ghosh Hima Mahor Uddipan Sarma Bhaskar Saha Residue-Specific Message Encoding in CD40-Ligand iScience Biochemical Mechanism Biochemistry Immunology |
| 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 | Biochemical Mechanism Biochemistry Immunology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004220306337 |
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