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

ABSTRACT: 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.

SUBMITTER: Brown LV 

PROVIDER: S-EPMC5908537 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature