MHC class I / II restricted T cell epitopes from clinical isolate of Mycobacterium tuberculosis: A potential candidate for vaccine development for Tuberculosis

Abstract

Tuberculosis is major challenge to the health care system with TB associated death rates increasing annually. Optimum management of TB (particularly latent or MDR cases) warrants use of immunological approaches like subunit or peptide-based vaccination for tailoring effector immunity in patients. Since MHC class I is a potent enhancer element of host immunity and effective in clearing large variety of intracellular pathogens or tumors. In this context, we explore whether MHC-I restricted peptides from clinical isolates of M. tuberculosis can be used as an adjuvant for augmenting host immune responses. In the present study, we have synthesized various peptides from clinical isolates of M. tuberculosis which were having high affinity for Class I MHC molecules as potential immune enhancer for T cell or iNKT cell populations. We have evaluated the immunogenic potential of various MHC class I restricted epitopes (Rv2588c, Rv1357, Rv0148, Rv2973, Rv2557 and Rv2445) which were derived from clinical isolates of M. tuberculosis on increased proliferation of T or iNKT cells, release of IFN gamma secreted by T cells as well as NO as indicative parameters of immuno-stimulation. As expected, FACS and ELISA data clearly revealed that these peptides were potentially immunogenic for PBMCs from both healthy as well as 10 HC PTB patients. Our data clearly demonstrated a significant immune response in the PBMC from w PTB patients over healthy individuals which mimicked booster response. Our cytokine and nitric oxide data further revealed the influence of these peptides on sensitizing innate immune response as well. SignificanceOur study demonstrates the significance of MHC class I restricted peptides from M. tuberculosis for inducing potential immunogenic responses in host that may qualify them as potent vaccine candidate. To the best of our knowledge this is the first immune monitoring protocol describing the impact of synthetic novel MHC class I restricted T-cell epitope (Rv2588c, Rv0148) on cell mediated and innate immune response in PBMC populations and suggests their potential as vaccine candidate