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.