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Changing of Val47 to Asp47 or to Lys47 enhances the immunomodulatory activity of the human Interleukin-l peptide 47–55

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Abstract

The 47–55 domain of the maturehumanInterleukin-was predicted to be exposed by our computational analysis and confirmed to be so by comparing with X-ray crystallographic as well as nuclear magnetic resonance (NMR) spectroscopic data. Four peptides representing fully or part of this domain with sequences 47–55, 41–61, 45–61 and 50–66 were synthesized and tested for their ability to modulate in vivo, the humoral immune response of Balb/c mice to Shigella dysenteriae 116 kDa antigen(s). The smallest immunomodulatory peptide amongst them was found to be the nonapeptide 47–55. To ascertain the structure-function relationships of this 47–55 peptide, various mutant peptides were synthesized and tested for IL-1β 2 like activity in vivo. Change of Val47 to Asp47 or to Lys47 enhanced its immunomodulatory activity significantly while the change of Gly49 to Asp49 or Glu50 to Ile50 or Asp54 to Ile54 had no such effect. The peptides 47–55 and its mutants were first tested for their ability to elicit inflammatory response like PGE2 synthesis by a sensitive radioimmunoassay. The peptides which did not have any inflammatory activity were then tested for their ability to stimulate antigen primed T-cells in vitro in the presence of sub-optimal concentration of the antigen.

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Correspondence to M. Bruhaspathy.

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Bruhaspathy, M., Kar, S.K. Changing of Val47 to Asp47 or to Lys47 enhances the immunomodulatory activity of the human Interleukin-l peptide 47–55. J. Biosci. 22, 77–89 (1997). https://doi.org/10.1007/BF02703620

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  • DOI: https://doi.org/10.1007/BF02703620

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