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Activity of the HMGB1-derived immunostimulatory peptide Hp91 resides in the helical C-terminal portion and is enhanced by dimerization
University of Calif San Diego, CA 92093 USA .
University of Calif San Diego, CA 92093 USA .
University of Calif San Diego, CA 92093 USA .
University of Calif San Diego, CA USA .
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2014 (English)In: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 57, no 2, 191-199 p.Article in journal (Refereed) Published
Abstract [en]

We have previously shown that an 18 amino acid long peptide, named Hp91, whose sequence corresponds to a region within the endogenous protein HMGB1, activates dendritic cells (DCs) and acts as adjuvant in vivo by potentiating Thl -type antigen-specific immune responses. We analyzed the structure-function relationship of the Hp91 peptide to investigate the amino acids and structure responsible for immune responses. We found that the cysteine at position 16 of Hp91 enabled formation of reversible peptide dimmers, monomer and dimmer were compared for DC binding and activation. Stable monomers and dimers were generated using a maleimide conjugation reaction. The dimer showed enhanced ability to bind to and activate DCs. Furthermore, the C-terminal 9 amino acids of Hp91, named UC1018 were sufficient for DC binding and Circular dichroism showed that UC1018 assumes an alpha-helical structure. The ninemer peptide UC1018 induced more potent antigen-specific CTL responses in vivo as compared to Hp91 and it protected mice from tumor development when used in a prophylactic vaccine setting. We have identified a short alpha helical peptide that acts as potent adjuvant inducing protective immune responses in vivo.

Place, publisher, year, edition, pages
Elsevier , 2014. Vol. 57, no 2, 191-199 p.
Keyword [en]
Peptide; Adjuvant; Immune response; Dendritic cells
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-103711DOI: 10.1016/j.molimm.2013.09.007ISI: 000329145800017OAI: diva2:690715
Available from: 2014-01-24 Created: 2014-01-24 Last updated: 2014-06-04

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Larsson, M.
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Division of Microbiology and Molecular MedicineFaculty of Health Sciences
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Molecular Immunology
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