Proteome-wide B and T cell epitope repertoires in outer membrane proteins ofMycobacterium aviumsubsp.paratuberculosishave vaccine and diagnostic relevance: a holistic approach

Abstract

Mycobacterium avium subsp. paratuberculosis (MAP) is an etiological agent of chronic inflammation of the intestine among ruminants and humans. Currently, there are no effective vaccines and sensitive diagnostic tests available for its control and detection. For this, it is of paramount importance to identify the MAP antigens, which may be immunologically recognized by the host immune system. To address this challenge, we performed identification of the immunogenic epitopes in the MAP outer membrane proteins (OMPs). We have previously identified 57 MAP proteins as OMPs [Rana A, Rub A, Akhter Y. 2014. Molecular BioSystems, 10:2329-2337] and have evaluated them for the epitope selection and analysis employing a computational approach. Thirty-five MAP OMPs are reported with nine-mer peptides showing high binding affinity to major histocompatibility complex (MHC) class I molecules and 28 MAP OMPs with 15-mer peptides of high binding affinity for MHC class II molecules. The presence of MHC binding epitopes indicates the potential cell-mediated immune response inducing capacity of these MAP OMPs in infected host. To further investigate the humoral response inducing properties of OMPs of MAP, we report potential B cell epitopes based on the sequences of peptide antigens and their molecular structures. We also report 10 proteins having epitopes for both B and T cells representing potential candidates which may invoke both humoral and cellular immune responses in the host. These findings will greatly accelerate and expedite the formulation of effective and cost-efficient vaccines and diagnostic tests against MAP infection.

In silico Identification of Potential Peptides or Allergen Shot Candidates Against Aspergillus fumigatus

“…The hit with an expectation value (E-value) less than 10 −4 was excluded from the analysis and these protein sequences were assumed to have high sequence similarity with the host and model organism's proteome. 18 …”

“…We considered only lower IC50 value epitopes because lower value indicates higher binding affinity of epitopes with host MHC alleles. We used all mouse MHC class I alleles (H-2-Db, H-2-Dd, H-2-Kb, H-2-Kd, H-2-Kk, and H-2-Ld) 18 and eight human MHC class I alleles that cover about 85–90% of the world population (A*0101, A*0201, A*2402, A*0301, A*1101, B*0702, B*0801, and B*1501). The epitopes for T cell MHC class I alleles were identified by submitting the FASTA format of allergenic protein sequence to IEDB-AR.…”

“…The artificial neural network (ANN) method was used to predict nine-mer sequence MHC class I epitopes. 18 …”

“…Mouse MHC class II and MHC class I T cell epitopes were predicted because common epitopes that recognize both human and mouse MHC T cell epitopes might be tested on model organism for their therapeutic potential and their results can be tested on human subjects. 18 Another purpose for screening of epitopic peptides of antigens from A. fumigatus with no homologs in humans is that they recognize both MHC class I and MHC class T cells of human. Other than vaccine or allergy shot candidate, such peptides can be directly used ex vivo for the development of A. fumigatus -specific T cells (Asp-STs) for adoptive immunotherapy of invasive aspergillosis in the allogeneic hematopoietic stem cell transplant individuals having hematopoietic malignancies.…”

A tug-of-war between the host and the pathogen generates strategic hotspots for the development of novel therapeutic interventions against infectious diseases

“…These OMPs have been targeted as potential antigenic candidates for identifying suitable epitopes for the formulation of vaccines against the Mycobacterium spp. 72 Some of the bacterial pathogens have the ability to resist the effects of antimicrobial compounds like antibiotics used against the bacterial infections. It is often mediated by other surface associated proteins like the Integral Membrane Proteins (IMPs) commonly expressed as ATP-binding cassette transporters (ABC) like protein, TonB dependent siderophore receptors and Multi-Drug Resistance (MDR) Efflux system protein which represent promising targets against drug resistant bacterial infections.…”