MMP-7 derived peptides with MHC class-I binding motifs from canine mammary tumor tissue elicit strong antigen-specific T
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MMP‑7 derived peptides with MHC class‑I binding motifs from canine mammary tumor tissue elicit strong antigen‑specific T‑cell responses in BALB/c mice Pavan Kumar Yadav1,2 · Shishir Kumar Gupta1,3 · Saroj Kumar1,2 · Mayukh Ghosh2 · Brijesh Singh Yadav1,4 · Dinesh Kumar1,5 · Ajay Kumar1 · Mohini Saini1 · Meena Kataria1 Received: 1 May 2020 / Accepted: 7 September 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Matrix Metalloproteinases (MMPs)-induced altered proteolysis of extracellular matrix proteins and basement membrane holds the key for tumor progression and metastasis. Matrix metalloproteinases-7 (Matrilysin), the smallest member of the MMP family also performs quite alike; thus serves as a potential candidate for anti-tumor immunotherapy. Conversely, being an endogenous tumor-associated antigen (TAA), targeting MMP-7 for immunization is challenging. But MMP-7-based xenovaccine can surmount the obstacle of poor immunogenicity and immunological tolerance, often encountered in TAA-based conventional vaccine for anti-tumor immunotherapy. This paves the way for investigating the potential of MMP-7-derived major histocompatibility complex (MHC)-binding peptides to elicit precise epitope-specific T-cell responses towards their possible inclusion in anti-tumor vaccine formulations. Perhaps it also ushers the path of achieving multiple epitope-based broad and universal cellular immunity. In current experiment, an immunoinformatics approach has been employed to identify the putative canine matrix matelloproteinases-7 (cMMP-7)-derived peptides with MHC class-I-binding motifs which can elicit potent antigen-specific immune responses in BALB/c mice. Immunization with the cMMP-7 DNA vaccine induced a strong CD8+ cytotoxic T lymphocytes (CTLs) and Th1- type response, with high level of gamma interferon (IFN-γ) production in BALB/c mice. The two identified putative MHC-I-binding nonameric peptides (Peptide32-40 and Peptide175-183) from cMMP-7 induced significant lymphocyte proliferation along with the production of IFN-γ from C D8+ T-cells in mice immunized with cMMP-7 DNA vaccine. The current observation has depicted the immunogenic potential of the two cMMP7-derived nonapeptides for their possible exploitation in xenovaccine-mediated anti-tumor immunotherapy in mouse model. Keywords Immunoinformatics · Mammary tumor · Matrix metalloproteinase-7 · Major histocompatibilty complex · Xenogeinic DNA vaccine
Introduction * Pavan Kumar Yadav [email protected]; [email protected] 1
ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh 243122, India
2
Faculty of Veterinary and Animal Sciences, Rajiv Gandhi South Campus, Banaras Hindu University, Mirzapur, Uttar Pradesh 231001, India
3
Laboratory Animal Facility, CSIR-CDRI, Lucknow, Uttar Pradesh 226031, India
4
University of Information Science & Technology St. Paul the apostle Partizanska bb., 6000 Ohrid, Republic of Macedonia
5
College of Agriculture, Tikamgarh, Jawaharlal Nehru Krishi
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