The Th Cell Types And Their Immunoprotection Induced By A CD4~+ T Cell Epitope In Staphylococcus Aureus FnbpA

Staphylococcus aureus(S.aureus)is one of the most important Gram-positive pathogens causing superficial skin lesions or even life-threatening invasive infections severe infection.CD4~+ T-cell plays an essential role in protection against Staphylococcus aureus infection.Fibronectin-binding protein A(FnbpA)is a crucial protein of S.aureus adhesion to host extracellular matrix proteins including fibronectin and fibrinogen,and can induce a strong Th1 and Th17 response after immunization of mice.And up to now,the CD4~+ T cell epitope,epitope-inducing Th cell types and their immunoprotection are still not clear.In this experiment,MHCII binding assay was used to predict CD4~+ T-cell epitopes in FnbpA of S.aureus,and seven epitope peptides were synthesized and used for validating the potential epitopes.We identified an immunodominant epitope,F5(488RGYTLTWDNGLVLYS NKA505),in FnbpA.The epitope could significantly induce CD4~+ T-cell proliferation and elicit high level of IFN-?production and moderate level of IL-17 production.In addition,this epitope F5 is determined as I-A MHC?restricted epitope and highly conserved in S.aureus strains.Based on the above research,the characterization of CD4~+ T-cell epitopes in FnbpA and its correlation with protection are vital to understanding anti-S.aureus immune responses.BALB/c mice were immunized with FnbpA protein and F5 emulsified with Freund adjuvant,the Th cell types were detected by flow cytometry.FnbpA-and F5 epitope-specifc Th1 and Th17 cells were isolated and adoptively transferred into na?ve mice,and then immunoprotection against S.aureus challenge provided by the transferred Th cells was detected.The results showed that both FnbpA and F5 epitope could induce strong Th1 response and and less strong Th17 response,and Th1-transferred mice could significantly defense against S.aureus challenge but Th17-transferred mice could not defense against S.aureus challenge so well.These results may provide useful insights into the mechanisms of anti-S.aureus immunity and development of vaccine against S.aureus infection.