An in silico model of cytotoxic T-lymphocyte activation in the lymph node following short peptide vaccination

作者：Brown Liam V^*; Gaffney Eamonn A; Wagg Jonathan; Coles Mark C

来源：Journal of the Royal Society Interface, 2018, 15(140): 20180041.

DOI：10.1098/rsif.2018.0041

• lymph node
• cancer vaccine
• antigen presentation
• modelling and simulation
• T-cell dynamics
• cytotoxic T-Lymphocyte activation

Tumour immunotherapy is dependent upon activation and expansion of tumour-targetting immune cells, known as cytotoxic T-lymphocytes (CTLs). Cancer vaccines developed in the past have had limited success and the mechanisms resulting in failure are not well characterized. To elucidate these mechanisms, we developed a human-parametrized, in silico, agent-based model of vaccination-driven CTL activation within a clinical short-peptide vaccination context. The simulations predict a sharp transition in the probability of CTL activation, which occurs with variation in the separation rate (or off-rate) of tumour-specific immune response-inducing peptides (cognate antigen) from the major histocompatibility class I (MHC-I) receptors of dendritic cells (DCs) originally at the vaccination site. For peptides with MHC-I off-rates beyond this transition, it is predicted that no vaccination strategy will lead to successful expansion of CTLs. For slower off-rates, below the transition, the probability of CTL activation becomes sensitive to the numbers of DCs and T cells that interact subsequent to DC migration to the draining lymph node of the vaccination site. Thus, the off-rate is a key determinant of vaccine design.

• 出版日期2018-3