Nowadays, it is found that S. aureus-stimulated humoral immune
response may not play a meaningful role in bacterial clearance.
The importance of T-cells and T-cell cytokines in innate
immunity to S. aureus has been the object of investigation [14e17].
The CD4þ T-cells not B-cells were the critical effector cells conferring
enhanced survival following S. aureus challenge in the BALB/c
murine sepsis model immunized with IsdB [13]. These events
support the potential of the IsdB as a target antigen for S. aureus
vaccine development, and promote us to investigate the protective
mechanism of CD4þ T-cell-mediated immunity. CD4þ T-cells are
primed by T-cell epitope peptides to differentiate into Th1 and Th17
type cells, both of which play central roles in protecting the host
against S. aureus infections [17]. However, little is known about the
specific IsdB CD4þ T-cell epitopes and its mechanisms involved in
the antigen-specific protective immunity.
The purpose of this study was to identify and validate IsdB
epitopes of CD4þ T-cell and to characterize CD4þ T-cell responses in
subjects with BALB/c and C57BL/6 mice representing H-2d and H-2b
types of MHC class II molecules. Using an in vitro MHC-peptide
binding assay as well as ex vivo proliferation and cytokine release
assays, we have identified and validated 2 epitopes restricted to
multiple MHC class II alleles. We also demonstrated that these
epitopes exert functional responses in a specific manner, capable of
inducing CD4þ T-cell proliferation and eliciting predominant production
of IFN-g and IL-17A cytokines. Our study provides important
data for the further design of IsdB epitope peptide-based
S. aureus vaccines.
Nowadays, it is found that S. aureus-stimulated humoral immuneresponse may not play a meaningful role in bacterial clearance.The importance of T-cells and T-cell cytokines in innateimmunity to S. aureus has been the object of investigation [14e17].The CD4þ T-cells not B-cells were the critical effector cells conferringenhanced survival following S. aureus challenge in the BALB/cmurine sepsis model immunized with IsdB [13]. These eventssupport the potential of the IsdB as a target antigen for S. aureusvaccine development, and promote us to investigate the protectivemechanism of CD4þ T-cell-mediated immunity. CD4þ T-cells areprimed by T-cell epitope peptides to differentiate into Th1 and Th17type cells, both of which play central roles in protecting the hostagainst S. aureus infections [17]. However, little is known about thespecific IsdB CD4þ T-cell epitopes and its mechanisms involved inthe antigen-specific protective immunity.The purpose of this study was to identify and validate IsdBepitopes of CD4þ T-cell and to characterize CD4þ T-cell responses insubjects with BALB/c and C57BL/6 mice representing H-2d and H-2btypes of MHC class II molecules. Using an in vitro MHC-peptidebinding assay as well as ex vivo proliferation and cytokine releaseassays, we have identified and validated 2 epitopes restricted tomultiple MHC class II alleles. We also demonstrated that theseepitopes exert functional responses in a specific manner, capable ofinducing CD4þ T-cell proliferation and eliciting predominant productionof IFN-g and IL-17A cytokines. Our study provides importantdata for the further design of IsdB epitope peptide-basedS. aureus vaccines.
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