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Bannantine, J. P.

Publications and source records attributed to Bannantine, J. P..

2 recordsLinked to original sources

Vaccination of cattle with a virus-vectored vaccine against a major membrane protein of Mycobacterium a. subsp. paratuberculosis elicits CD8 cytotoxic T cells that kill intracellular bacteria

Infection of cattle with Mycobacterium a. subsp. Paratuberculosis (Map), the causative agent of paratuberculosis, induces an immune response directed toward a 35 kD major membrane protein (MMP) of Map. CD8 cytotoxic T cells (CTL) are elicited when peripheral blood mononuclear cells from healthy cattle are incubated ex vivo with antigen-presenting cells (APC) primed with bacterial recombinant MMP. Ex vivo development of CTL was MHC-restricted and required the presence of both CD4 and CD8 T cells. The gene MAP2121c, encoding MMP, was modified to express a modified form of MMP (p35NN) in a mammalian cell line, also capable of eliciting an ex vivo CTL response. In the present study, the modified gene for p35NN was placed into a BoHV4 vector to determine the potential use of BoHV-4A{Delta}TK-p35NN as a peptide-based vaccine. Subcutaneous vaccination of healthy cattle with BoHV-4A{Delta}TK-p35NN elicited a CTL recall response, as detected ex vivo. Further studies are warranted to conduct a challenge study to determine if CD8 CTL elicited by vaccination with BoHV-4A{Delta}TK-p35NN prevents the establishment of a persistent infection by Map.

immunology↗

Cognate epitope recognition by bovine CD4 and CD8 T cells is essential for primary expansion of antigen-specific cytotoxic T-cells following ex vivo stimulation with a candidate Mycobacterium avium subsp. paratuberculosis peptide vaccine.

Studies in cattle show CD8 cytotoxic T cells (CTL), with the ability to kill intracellular bacteria, develop following stimulation of monocyte-depleted peripheral blood mononuclear cells (mdPBMC) with conventional dendritic cells (cDC) and monocyte-derived DC (MoDC) pulsed with MMP, a membrane protein from Mycobacterium avium subsp. paratuberculosis (Map) encoded by MAP2121c. CTL activity was diminished if CD4 T cells were depleted from mdPBMC before antigen (Ag) presentation by cDC and MoDC, suggesting simultaneous cognate recognition of MMP epitopes presented by MHC I and MHC II molecules might be essential for development of CTL activity. To clarify whether cognate recognition is essential for CTL development, studies were conducted with mdPBMC cultures in the presence of monoclonal antibodies (mAbs) specific for MHC class I and MHC class II molecules. The CTL response of mdPBMC to MMP-pulsed DC was completely blocked in the presence of mAbs to both MHC I and II molecules and also blocked in the presence of mAbs to either MHC I or MHC II. The results demonstrate CD4 T-cell help is essential for development of a primary CTL response to MMP, and indicate that cognate recognition is required for delivery of CD4 T-cell help during priming. Of importance, the findings provide support for the importance of CD4 and CD8 T-cell cognate antigen recognition in eliciting CTL responses to vaccines against intracellular pathogens. The methods described herein can be used to elucidate the intracellular interactions between lymphocytes and DC in humans and cattle.

immunology↗