CTLA-4-Mediated Ligand Trans-Endocytosis: A Stochastic Model

Competition between CTLA-4 and CD28 co-receptors for the ligands B7-1 and B7-2 determines the balance between co-stimulation, important for effective CD4+ T-cell immune responses, and negative regulation, important to avoid autoimmunity. CTLA-4, less abundant than CD28 on the surface of resting conventional naive T cells, is trafficked to the surface of activated T cells from intracellular endosomes. We introduce a stochastic model of the binding and internalisation dynamics of CTLA-4 and analyse its behaviour making use of different stochastic descriptors defined in a matrix formalism. We compare and contrast the dynamics of the interaction of CTLA-4 with B7-1 and B7-2 and of B7-1 and B7-2 ligand trans-endocytosis, separately and in competition.