Identification of CD4+ T cell epitopes from Staphylococcus aureus secretome using immunoinformatic prediction and molecular docking

• Main Authors: Dileep Francis, Arun Kumar, Sadasivan Chittalakkottu
• Format: Article
• Language: English
• Published: Termedia Publishing House 2021-03-01
• Series: BioTechnologia
• Subjects: cd4+ t cell; epitope prediction; secretory proteins; staphylococcus aureus; peptide vaccine; molecular docking
• Online Access: https://www.termedia.pl/Identification-of-CD4-T-cell-epitopes-from-Staphylococcus-aureus-secretome-using-immunoinformatic-prediction-and-molecular-docking,85,43336,1,1.html
• ISSN: 0860-7796; 2353-9461

One major reason for the lack of clinical success of Staphylococcus aureus vaccine candidates is the inability of the antigens to develop a CD4+ T cell-mediated immune response. Hence, it is important to identify CD4+ T cell anti¬gens from S. aureus. CD4+ T cells are activated following the presentation of epitopes derived from exogenous proteins on HLA class II molecules. Fifty-nine secretory proteins of S. aureus were analyzed computationally for the presence of HLA class II binding peptides. Fifteen-mer peptides were generated, and their binding to 26 HLA class II alleles was predicted. The structural feasibility of the peptides binding to HLA-II was studied using mole¬cular docking. Of the 16,724 peptides generated, 6991 (41.8%) were predicted to bind to any one of the alleles with an IC50 value below 50 nM. Comparative sequence analysis revealed that only 545 of the strong binding pe¬ptides are non-self in the human system. Approximately 50% of the binding peptides were monoallele-specific. Moreover, approximately 95% of the predicted strong binding non-self peptides interacted with the binding groove of at least one HLA class II molecule with a glide score better than −10 kcal/mol. On the basis of the ana¬lysis of the strength of binding, non-self presentation in the human host, propensity to bind to a higher number of alleles, and energetically favorable interactions with HLA molecules, a set of 11 CD4+ T cell epitopes that can be used as vaccine candidates was identified.