Immunogenicity of MHC Class I Peptides Derived from Leishmania mexicana Gp63 in HLA-A2.1 Transgenic (HHDII) and BALB/C Mouse Models
Abstract
Background: Leishmania is an intracellular parasite infecting humans and many wild and domestic animals. Recent studies have suggested an important role for cytotoxic T cells against Leishmania. Peptide-based vaccines targeting short sequences derived from known immunogenic proteins have been shown to elicit cellular immune responses against disparate pathogens.
Methods: We predicted four HLA-A2 peptides derived from L. mexican/major gp63 and tested these in HHD II mice, as well as four peptides for mouse MHC class I from the same proteins tested in BALB/ mice.
Results: The results revealed immunogenicity for three of the four peptides predicted for HLA-A2.Immunisation with these peptides, along with IFA, induced CTL responses detected by standard 4- hour cytotoxicity assay and significantly upregulated the production of IFN-γ. When HHDII mice were injected IM with L. mexicana gp63 cDNA and splenocytes were restimulated with blasts loaded with the immunogenic peptides, two of the peptides were able to induce significant level of IFN-γ detected by ELISA. None of the peptides predicted for Balb/c mouse MHC class I elicited CTL ac- tivity or significantly upregulated the IFN-γ.
Conclusion: The results may help in developing a peptide-based vaccine, which can be applied alone or in combination with drugs against Leishmania.
WHO. Leishmaniasis; Strategic direction for research: [http://www.who.int/tdr/diseases/leish/dire ction.htm].
Griekspoor A, Sondorp E, Vos T. Costeffectiveness analysis of humanitarian relief interventions: visceral leishmaniasis treatment in the Sudan. Health Policy Plan. 1999; 14(1):70-76.
Desjeux P. Leishmaniasis: current situation and new perspectives. Comp Immunol Microbiol Infect Dis. 2004; 27(5):305-318.
Kar K. Serodiagnosis of leishmaniasis. Crit Rev Microbiol. 1995; 21(2):123-152.
Puig L, Pradinaud R. Leishmania and HIV coinfection: dermatological manifestations. Ann Trop Med Parasitol. 2003; 97 Suppl 1:107-114.
Sacks D, Noben-Trauth N. The immunology of susceptibility and resistance to Leishmania, major in mice. Nat Rev Immunol. 2002; 2(11):845-858.
Muller I, Kropf P, Etges RJ, Louis JA. Gamma interferon response in secondary Leishmania major infection: role of CD8+ T cells. Infect Immun. 1993; 61(9):3730-3738.
Rogers KA, DeKrey GK, Mbow ML, Gillespie RD, Brodskyn CI, Titus RG. Type 1 and type 2 responses to Leishmania major. FEMS Microbiol Lett. 2002; 209(1):1-7.
Erb K, Blank C, Ritter U, Bluethmann H, Moll H. Leishmania major infection in major histocompatibility complex class II-deficient mice: CD8+ T cells do not mediate a mprotective immune response. Immunobiology. 1996; 195(2):243-260.
Awasthi A, Mathur RK, Saha B. Immune response to Leishmania infection. Indian J Med Res. 2004; 119(6):238-258.
Rivier D, Bovay P, Shah R, Didisheim S, Mauël J. Vaccination against Leishmania major in a CBA mouse model of infection: role of adjuvants and mechanism of protection. Parasite Immunol. 1999;21(9):461-73.
Ali SA, Rezvan H, McArdle SE, Khodadadi A, Asteal FA, Rees RC. CTL responses to Leishmania mexicana gp63-cDNA vaccine in a murine model. Parasite Immunol. 2009; 31(7):373-383.
Coler RN, Reed SG. Second-generation vaccines against leishmaniasis. Trends Parasitol. 2005; 21(5):244-249.
Ahmad M, Rees RC, McArdle SE, Li G, Mian S, Entwisle C, Loudon P, Ali SA. Regulation of CTL responses to MHC-restricted class I peptide of the gp70 tumour antigen by splenic parenchymal CD4+ T cells in mice failing immunotherapy with DISC-mGM-CSF. Int J Cancer. 2005; 115(6):951-959.
Assudani DP, Ahmad M, Li G, Rees RC, Ali SA. Immunotherapeutic potential of DISCHSV and OX40L in cancer. Cancer Immunol Immunother. 2006; 55(1):104-111.
Machado-Pinto J, Pinto J, da Costa CA, Genaro O, Marques MJ, Modabber F, Mayrink W. Immunochemotherapy for cutaneous leishmaniasis: a controlled trial using killed Leishmania (Leishmania) amazonensis vaccine plus antimonial. Int J Dermatol. 2002; 41(2):73-78.
Stanekova Z, Vareckova E. Conserved epitopes of influenza A virus inducing protective immunity and their prospects for universal vaccine development. Virol J. 2010.
Fiorentini S, Marsico S, Becker PD, Iaria ML, Bruno R, Guzman CA, Caruso A. Synthetic peptide AT20 coupled to KLH elicits antibodies against a conserved conformational epitope from a major functional area of the HIV-1 matrix protein p17. Vaccine. 2008; 26(36):4758-4765.
Bates PA. Complete developmental cycle of Leishmania mexicana in axenic culture. Parasitology. 1994; 108 ( Pt 1):1-9.
Ali S, Ahmad M, Lynam J, Rees RC, Brown N. Trafficking of tumor peptide-specific cytotoxic T lymphocytes into the tumor microcirculation. Int J Cancer. 2004; 110(2):239-244.
Saren A, Pascolo S, Stevanovic S, Dumrese T, Puolakkainen M, Sarvas M, Rammensee HG, Vuola JM. Identification of Chlamydia pneumoniae-derived mouse CD8 epitopes. Infect Immun. 2002; 70(7):3336-3343.
Hundemer M, Schmidt S, Condomines M, Lupu A, Hose D, Moos M, Cremer F, Kleist C, Terness P, Belle S et al. Identification of a new HLA-A2-restricted T-cell epitope within HM1.24 as immunotherapy target for multiple myeloma. Exp Hematol. 2006; 34(4):486-496.
Ramage JM, Metheringham R, Moss R, Spendlove I, Rees R, Durrant LG. Comparison of the immune response to a self antigen after DNA immunization of HLA*A201/H-2Kb and HHD transgenic mice. Vaccine. 2004; 22(13-14):1728-1731.
van der Bruggen P, Bastin J, Gajewski T, Coulie PG, Boel P, De Smet C, Traversari C, Townsend A, Boon T. A peptide encoded by human gene MAGE-3 and presented by HLA-A2 induces cytolytic T lymphocytes that recognize tumor cells expressing MAGE-3. Eur J Immunol. 1994; 24(12):3038-3043.
Firat H, Garcia-Pons F, Tourdot S, Pascolo S, Scardino A, Garcia Z, Michel ML, Jack RW, Jung G, Kosmatopoulos K et al. H-2 class I knockout, HLA-A2.1-transgenic mice: a versatile animal model for preclinical evaluation of antitumor immunotherapeutic strategies. Eur J Immunol. 1999; 29(10):3112.
Spitzer N, Jardim A, Lippert D, Olafson RW. Long-term protection of mice against nLeishmania major with a synthetic peptide vaccine. Vaccine. 1999; 17(11-12):1298-1300.
Engelhard VH, Bullock TN, Colella TA, Mullins DW. Direct identification of human tumor-associated peptide antigens and a npreclinical model to evaluate their use. Cancer J. 2000; 6 Suppl 3:S272-280.
Rojas JM, McArdle SE, Horton RB, Bell M, Mian S, Li G, Ali SA, Rees RC. Peptide immunisation of HLA-DR-transgenic mice permits the identification of a novel HLADRbeta1* 0101- and HLA-DRbeta1*0401- restricted epitope from p53. Cancer Immunol Immunother. 2005; 54(3):243-253.
Rammensee H, Bachmann J, Emmerich NP, Bachor OA, Stevanovic S. SYFPEITHI: database for MHC ligands and peptide motifs. Immunogenetics. 1999; 50(3-4):213-219.
Gurunathan S, Irvine KR, Wu CY, Cohen JI, Thomas E, Prussin C, Restifo NP, Seder RA. CD40 ligand/trimer DNA enhances both humoral and cellular immune responses and induces protective immunity to infectious and tumor challenge. J Immunol. 1998; 161(9):4563-4571.
Mishra S, Sinha S. Prediction and molecular modeling of T-cell epitopes derived from placental alkaline phosphatase for use in cancer immunotherapy. J Biomol Struct Dyn. 2006; 24(2):109-121.
Pelte C, Cherepnev G, Wang Y, Schoenemann C, Volk HD, Kern F. Random screening of proteins for HLA-A*0201- binding nine-amino acid peptides is not sufficient for identifying CD8 T cell epitopes recognized in the context of HLA-A*0201. J Immunol. 2004; 172(11):6783.
Mathieu MG, Knights AJ, Pawelec G, Riley CL, Wernet D, Lemonnier FA, Straten PT, Mueller L, Rees RC, McArdle SE. HAGE, a cancer/testis antigen with potential for melanoma immunotherapy: identification of several MHC class I/II HAGE-derived immunogenic peptides. Cancer Immunol Immunother. 2007; 56(12):1885-1895.
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Issue | Vol 7 No 4 (2012) | |
Section | Original Article(s) | |
Keywords | ||
HHDII Peptide Vaccine Leishmania |
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