A stochastic model of cytotoxic T cell responses

Dennis L. Chao, Miles P. Davenport, Stephanie Forrest, Alan S. Perelson

Research output: Contribution to journalArticle

77 Scopus citations

Abstract

We have constructed a stochastic stage-structured model of the cytotoxic T lymphocyte (CTL) response to antigen and the maintenance of immunological memory. The model follows the dynamics of a viral infection and the stimulation, proliferation, and differentiation of naïve CD8+ T cells into effector CTL, which can eliminate virally infected cells. The model is capable of following the dynamics of multiple T cell clones, each with a T cell receptor represented by a digit string. MHC-viral peptide complexes are also represented by strings and a string match rule is used to compute the affinity of a T cell receptor for a viral epitope. The avidities of interactions are also computed by taking into consideration the density of MHC-viral peptides on the surface of an infected cell. Lastly, the model allows the probability of T cell stimulation to depend on avidity but also incorporates the notion of an antigen-independent programmed proliferative response. We compare the model to experimental data on the cytotoxic T cell response to lymphocytic choriomeningitis virus infections.

Original languageEnglish (US)
Pages (from-to)227-240
Number of pages14
JournalJournal of Theoretical Biology
Volume228
Issue number2
DOIs
StatePublished - May 21 2004
Externally publishedYes

Keywords

  • Cytotoxic T lymphocyte
  • Immunological memory
  • Immunology
  • Stage-structured modeling

ASJC Scopus subject areas

  • Statistics and Probability
  • Modeling and Simulation
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)
  • Applied Mathematics

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