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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Antoni G, Presentini R, Perin F, Tagliabue A, Ghiara P, Censini S, Volpini G, Villa L and Boraschi D 1986 A short synthetic peptide fragment of human Interieukin-1 with immunostimulatory but not inflammatory activity;J. Immunol,137 3201–3204
Atherton E and Sheppard R C 1989Solid Phase Peptide Synthesis: A practical approach (Oxford: IRL Press)
Chou P Y and Fasman G D 1979 Prediction of beta turns;Biophys. J. 26 367–373
Clore G M, Wingfield P T and Gronenborn AM 1991 High-Resolution Three-Dimensional Structure of IL-1 in solution by Three- and Four-Dimensional Nuclear Magnetic Resonance Spectroscopy;Biochemistry 30 2315–2323
Dinarello A. A 1991 Interleukin-1 and Interleukin-1 antagonism;Blood 77 1627–1652
Driscoll P C, Gronenborn A M, Wingfield P T and Clore GM 1990 Determination of the secondary structure and molecular topology of Interleukin-1 by use of two and three dimensional heteronuclear15N-1HNMR spectroscopy;Biochemistry 29 4668–4682
Engvall E and Perlmann P 1972 Enzyme linked Immunosorbent assay (ELISA), III. Quantitation of specific antibodies by Enzyme labelled antiimmunoglobulin in antigen coated tubes;J. Immunol. 109 129–135
Falkoff R J M, Muraguchi A, Hong J X, Butler J L, Dinarello A. A and Fauci AS 1983 The effects of Interleukin-1 on human B cell activation and proliferation;J. Immunol. 131 801–805
Kaye J, Gillis S, Mizel S B, Shevac E M, Malek T R, Dinarello A. A, Lachman L B and Janeway A. A Jr 1984 Growth of a cloned helper T cell line induced by a monoclonal antibody specific for the antigen receptor: Interleukin-1 is required for expression of receptor for Interleukin-2;J. Immunol. 133 1339–1345
Laemmli U K 1970 Cleavage of structural proteins during the assembly of head of bacteriophage T4;Natural (London) 227 680–685
Lowenthal J W, Cerottini JC and MacDonald HR 1986 Interleukin-1 dependent induction of both Interleukin-2 secretion and Interleukin-2 receptor expression by thymoma cells;J. Immunol. 137 1226–1231
Manivel V and Rao K V S 1991 Interleukin-1 derived synthetic peptide as an added coadjuvant in vaccine formulation;Vaccine 9 395–397
Nencioni L, Villa L, Tagliabue A, Antoni G, Presentini R, Perin F, Silvestri S and Boraschi D 1987 In-vivo immunostimulatory activity of the 163–171 peptide of humanIL-1 ∼;J. Immunol. 139 800–804
Pauletti D, Simmonds R, Dressman G R and Kennedy R C 1985 Application of a modified computer algorithm in determining potential antigenic determinants associated with the AIDS virus glycoproteins;Anal. Biochem. 151 540–546
Pike B L and NossalG J V 1985 Interleukin-1 can act as a B cell growth and differentiation factor;Proc. Natl. Acad. Sci. USA 82 8153–8157
Priestle J P, Schar H P and Grutter M G 1989 Crystallographic refinement of IL-1β at 2A resolution;Proc. Natl. Acad. Sci. USA 86 9667–9671
Rao K V S and Nayak A R 1990 Enhanced immunogenicity of a sequence derived from hepatitis B virus surface antigen in a composite peptide that includes the immunostimulatory region from human Interleukin-1;Proc. Natl. Acad. Sci. USA 87 5519–5522
Simon P L, Kumar V, Lillquist J S, Bhatnagar P, Einstein R, Lee J, Porter T, Green D, Sathe G and Young P R 1993 Mapping of neutralizing epitopes and the receptor binding site of human Interleukin-1β;J. Biol. Chem. 268 9771–9779
Staruch M J and Wood D D 1983 The adjuvanticity of Interleukin-1in vivo;J. Immunol. 130 2191–2194
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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