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

NIETO, FRANCO*; GARRIDO, FACUNDO* (PRIMERA AUTORÍA COMPARTIDA); DINAMARCA, SOFÍA; CEBRIAN, IGNACIO; MAYORGA, LUIS S.

CELLULAR IMMUNOLOGY

ACADEMIC PRESS INC ELSEVIER SCIENCE

Año: 2022 vol. 382

0008-8749

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 hypotheses and design experiments. In particular, the model predictions and the experimental results obtained indicate that the rate-limiting step in cross-presentation of soluble ovalbumin is MHC-I loading after proteasomal processing of the antigenic protein.