• Identification of immunodominant and conserved epitopes of heat shock protein 70 for cancer vaccine development
  • Matin Kayyal,1 Azam Bolhassani,2,*
    1. Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
    2. Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, Iran


  • Introduction: Heat shock proteins are carriers of tumor antigens that trigger innate immunity, which in turn activates the adaptive immune system. Therefore, these proteins can be used as adjuvants to stimulate the immune system and develop immunotherapy approaches in the treatment of cancer. Heat shock protein-70 (HSP70), as a powerful immunostimulatory agent, may function as a sort of link between innate and adaptive immune response and stimulate cellular immunity.
  • Methods: In this study, the immunodominant and conserved epitopes of heat shock protein 70 (Hsp70) as an immunostimulatory agent were analyzed using different bioinformatics and computational tools. For this purpose, the cytotoxic T-lymphocyte (CTL) and helper T-lymphocyte (HTL) epitopes were predicted by NetMHCpan 4.0, NetMHCIIpan and IEDB. Then, the epitopes with the highest binding affinity scores were selected. After that, population coverage was estimated by IEDB tools for each epitope. Next, toxicity and allergenicity were measured by ToxinPred and AlgPred web servers, respectively. Moreover, secretion of cytokines as an important step was evaluated by web servers which established by Raghava’s groups. Finally, for peptide-protein flexible Docking, GalaxyPepDock server was used to predict docking scores between MHC alleles and peptides.
  • Results: The CTL epitopes of HSP70 (113-FYPEEISSMVLTKM-126 and 285-SLFEGIDFYTSITR-298), and HTL epitopes of HSP70 (168-NVLRIINEPTAAAIA-18 and 389-QDLLLLDVAPLSLGL-403) were selected based on the immunoinformatics analysis. These epitopes showed high rates for inducing cytokines. The highest population coverage rates were 88.39% and 81.19% for CTL epitopes of HSP70285-298 and HSP70113-126, and 21.86% and 45.07% for HTL epitopes of HSP168-182 and HSP70389-403, respectively in the world’s population.
  • Conclusion: The immunodominant, conserved, non-allergenic, non-toxic and immunogenic epitopes of HSP70 proteins were determined for design of a cancer vaccine construct.
  • Keywords: Innate immunity, Adaptive immunity, Heat shock protein, Immunoinformatics tools