Simultaneous 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

Authors

• Gaber S. Abdellrazeq, Washington State University, Pullman & Alexandria University
• Lindsay M. Fry, USDA, ARS, Animal Disease Research Unit
• Mahmoud M. Elnaggar, Washington State University, Pullman &Alexandria University, Egypt
• J. P. Bannantine, USDA-ARS, National Animal Disease CenterFollow
• David A. Schneider, USDA, ARS, Animal Disease Research Unit
• William M. Chamberlin, Retired
• Asmaa H.A. Mahmoud, Washington State University, Pullman & Ministry of Agriculture and Land Reclamation, Egypt
• Kun-Taek Park, Inje University
• Victoria Hulubei, Washington State University, PullmanFollow
• William C. Davis, Washington State University, PullmanFollow

Document Type

Article

Date of this Version

2020

Citation

Vaccine 38 (2020) 2016–2025

https://doi.org/10.1016/j.vaccine.2019.12.052

Comments

U.S. government works are not subject to copyright.

Abstract

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 antigen-presenting cells (APC, i.e. conventional dendritic cells [cDC] and monocyte-derived DC [MoDC]) pulsed with MMP, a membrane protein from Mycobacterium avium subsp. paratuberculosis (Map) encoded byMAP2121c. CTL activity was diminished if CD4 T cells were depleted from mdPBMC before antigen (Ag) presentation by APC, suggesting simultaneous cognate recognition of MMP epitopes presented by MHC I and MHC II molecules to CD4 and CD8 T cells is essential for development of CTL activity. To explore this possibility, 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 APC 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 alone. The results demonstrate simultaneous cognate recognition of Ag by CD4 and CD8 T cells is essential for delivery of CD4 T cell help to CD8 T cells to elicit development of CTL.