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Residue-Specific Message Encryption in CD40-Ligand

38 Pages Posted: 3 Mar 2020 Publication Status: Published

See all articles by Aditya Sarode

Aditya Sarode

National Centre for Cell Science - Pathogenesis and Cellular Response

Mukesh Jha

National Centre for Cell Science - Pathogenesis and Cellular Response

Shubhranshu Zutshi

National Centre for Cell Science - Pathogenesis and Cellular Response

Soumyakanti Ghosh

National Centre for Cell Science - Pathogenesis and Cellular Response

Hima Mahour

National Centre for Cell Science - Pathogenesis and Cellular Response

Uddipan Sarma

National Centre for Cell Science - Pathogenesis and Cellular Response

Bhaskar Saha

National Centre for Cell Science - Pathogenesis and Cellular Response

More...

Abstract

CD40-Ligand (CD40L)-CD40 interaction regulates immune responses againstpathogens, autoantigens, tumor and transplantation antigens. Single amino acidmutations 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 encryption of a distinct set of messages that collectively define CD40L pleiotropy, serve as a target for engineering the ligand to generate superagonists as immunotherapeutics and implicate the evolutionary diversification of functions among the ligands in a protein superfamily.

Suggested Citation

Sarode, Aditya and Jha, Mukesh and Zutshi, Shubhranshu and Ghosh, Soumyakanti and Mahour, Hima and Sarma, Uddipan and Saha, Bhaskar, Residue-Specific Message Encryption in CD40-Ligand. Available at SSRN: https://ssrn.com/abstract=3543839 or http://dx.doi.org/10.2139/ssrn.3543839
This version of the paper has not been formally peer reviewed.

Aditya Sarode

National Centre for Cell Science - Pathogenesis and Cellular Response ( email )

India

Mukesh Jha

National Centre for Cell Science - Pathogenesis and Cellular Response

India

Shubhranshu Zutshi

National Centre for Cell Science - Pathogenesis and Cellular Response

India

Soumyakanti Ghosh

National Centre for Cell Science - Pathogenesis and Cellular Response

India

Hima Mahour

National Centre for Cell Science - Pathogenesis and Cellular Response

India

Uddipan Sarma

National Centre for Cell Science - Pathogenesis and Cellular Response

India

Bhaskar Saha (Contact Author)

National Centre for Cell Science - Pathogenesis and Cellular Response ( email )

India

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