Per a 5 derived T cell peptides modulate NF-kB signalling to ameliorate allergic inflammation systemically in murine model of cockroach allergic hyper-reactivity.
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Peptide immunotherapy (PIT) represents a safe and efficacious therapeutic regimen with in-consequential side-effects. Present study aims to identify T cell epitopes of Per a 5 allergen, a delta class GST from Periplaneta americana and investigate effect of peptide treatment in murine model of cockroach allergen mediated hyper-reactivity. The epitopes (TC-P1, TC-P2 & TC-P3) were identified as promiscuous MHC-II binders by MHC-Pred, ProPred & IEDB analysis tool. Murine model of cockroach allergic hyper-reactivity was generated in Balb/c mice. A marked reduction in cellular infiltration in lungs (3-fold compared to Non-IT) was observed in T3-IT group as evidenced by total leucocyte count in BALF and histology. Specific IgE levels were reduced 3-fold in T2-IT and T3-IT compared to Non-IT with increase in IgG2a levels. IL-4 and IL-13 were reduced upto 2.5-fold in treatment groups compared to Non-IT group. Splenocytes revealed significant increase in levels of CD4 +FoxP3 + T cells in TC-P1 and TC-P2 mice demonstrating a systemic shift towards Tregs. Peptide treatment downregulated NF-kB signalling in lung and enhanced the levels of immune-regulatory molecules α1-antitrypsin and elafin. Our results indicate that, TC-P1 and TC-P3 alter Th2 cytokine milieu and antibody isotype ratio to suppress allergic inflammation. PIT modulates local and systemic mechanisms to resolve inflammation and possess potential for treatment in cockroach allergy.