Cosma and Eisenlohr comprehensively reviewed the multiple layers of how the T cell immune response is impacted by epitope density. After reviewing the mechanics of TCR-pMHC interaction (synapse/kinapse formation and kinetics; TCR microcluster formation and the serial engagement model; the distinctions between affinity, avidity and functional avidity), they tackle the context-dependent role and tradeoffs of epitope density in determining: naive vs. antigen-experienced T cell stimulation, avidity and functional avidity, stimulation of proliferation and cytotoxicity, immunodominance, CD4+ and CD8+ distinctions, and memory cell formation.
Effective immune responses against intracellular pathogens and tumors frequently rely upon CD8+ cytotoxic T lymphocytes (CTLs). In turn, CTL detection of foreign material from viruses and bacteria depends on antigen presentation by the MHC class I pathway. The underpinnings of antigen processing and presentation and, subsequent T cell activation and immunological memory development, have been extensively studied, leading to a better understanding of the balance between antigen dose, context, and, the T cell activation threshold. Still, the complexity of this process leads to apparent contradictions that hinder construction of rational strategies for generating optimal CD8 + T cell responses in a variety of settings. In this review we consolidate the current knowledge around the effects of peptide MHC I complex (pMHC) density and kinetics on CD8 + T cell responses and function during the acute phase of an infection.