Kinetics of antigen cross-presentation assessed experimentally and by a model of the complete endomembrane system

FACUNDO GARRIDO; FRANCO NIETO; SOFÍA DINAMARCA; IGNACIO CEBRIÁN; LUIS S. MAYORGA

Mar del Plata

Congreso; Reunión Anual de Sociedades de Biociencias 2022; 2022

SAIC-SAI-FAIC-SAFIS

Dendritic cells (DCs) have a specialized endomembrane system capable of presenting exogenous antigens in the context of MHC class I (MHC-I) molecules. This process, named cross presentation, is crucial to activate CD8+ T lymphocytes and initiate cytotoxic immune responses. In this report, we present an Agent Based Model in combination with Ordinary Differential Equations with enough complexity to reproduce cross-presentation. The model embraces the secretory and endocytic pathways, in connection with the plasma membrane, the endoplasmic reticulum and the cytosol. Key molecules required for cross-presentation were included as cargoes. In the simulations, the kinetics of MHC-I uptake and recycling, and cross-presentation accurately reproduced experimental values. The model proved to be a suitable tool to elaborate hypothesis and design experiments. In particular, the model predictions and the experimental results obtained indicate that the rate-limiting step in cross-presentation is the loading of complexes after the proteasomal processing of the antigenic proteins.