PS-328 Prediction Of Human Promiscuous Mhc Class I Restricted Cd8 + T-cell Epitopes In The Ppe Protein Family Of Mycobacterium Tuberculosis: A Computational Approach

Abstract

Background and aims Tuberculosis (TB), caused by infection with Mycobacterium tuberculosis, is a major cause of morbidity and mortality worldwide. Although the wide use of Mycobacterium bovis bacille Calmette-Guérin (BCG), the true effectiveness of BCG vaccine has been debated for decades. Others, the sensitivity of both tuberculin skin test and IFN-γ-release assays is suboptimal, and none of these tests distinguish between latent infection and active disease. So, there is a pressing need to detect new TB antigens to develop effective vaccines capable of activating the immune responses relevant for protection and to set up sensitive immunological tests that may improve the identification of latent TB. Methods In this study, through database access to the DNA and protein sequences of PPE proteins and the use of bioinformatics programs, including SignalP4.1 server, SecretomeP 2.0 server, DAS server and NetMHC3.4 server, promiscuous epitope peptides were identified. Results We identified four promiscuous epitope peptides. Those four peptides can bind to more than two HLA molecules. Three peptides were obtained from PPE8 protein and one from PPE12 protein. PPE8 might turn out as a useful reagent for TB subunit vaccines and diagnostic antigens. ![Abstract PS-328 Figure 1][1] Abstract PS-328 Figure 1 Signal peptide prediction. (A)The presence of a signal peptide in protein PPE16, where S-mean indicates the amino acids that are most likely to compose the signal peptide, and Y-max indicates the cleavage site. (B) No signal peptide was found in protein PPE33, as indicated by arrow. ![Abstract PO-0305 Figure 2][1] Abstract PO-0305 Figure 2 Analysis of transmembrane helices. No transmembrane helice was found in protein PPE16 between the cleavage site (P29) and the N-terminus, as indicated by arrow. Conclusions Prediction analysis showed that these promiscuous epitope peptides presented here may be important targets in the search for subunit vaccines or diagnostic antigens against Mycobacterium tuberculosis. Additionally, we suggest that these peptides may be used in immunological assays to evaluate the level of protection, the effect on pathology reduction and the profile of cytokines and antibodies induced by them. View this table: Abstract PS-328 Table 1 +T cell epitopes from PPE proteins of M.tuberculosis predicted by using Net.4 Server Note: 1 represents the total number of the epitopes of each protein; 2 the left of the solidus represents the number of strong-bind epitopes; the right represents the number of weak-bind epitopes. View this table: Abstract PS-328 Table 2 Distribution of promiscuous+T cell epitopes [1]: pending:yes