https://pure.iiasa.ac.at/id/eprint/4236 2021-08-27T17:35:54Z info:eu-repo/semantics/descriptiveMetadata https://pure.iiasa.ac.at/id/eprint/4236/ Antigenic oscillations and shifting immunodominance in HIV-1 infections Nowak, M.A. May, R.M. Sigmund, K. Atypical protein antigen contains several epitopes that can be recognized by cytotoxic T lymphocytes (CTL), but in a characteristic antiviral immune response in vivo, CTL recognize only a small number of these potential epitopes, sometimes only one, this phenomenon is known as immunodominance. Antigenic variation within CTL epitopes has been demonstrated for the human immunodeficiency virus HIV-1 and other viruses and such 'antigenic escape' may be responsible for viral persistence. Here we develop a new mathematical model that deals with the interaction between CTL and multiple epitopes of a genetically variable pathogen, and show that the nonlinear competition among CTL responses against different epitopes can explain immunodominance. This model suggests that an antigenically homogeneous pathogen population tends to induce a dominant response against a single epitope, whereas a heterogeneous pathogen population can stimulate complicated fluctuating responses against multiple epitopes. Antigenic variation in the immunodominant epitope can shift responses to weaker epitopes and thereby reduce immuno-logical control of the pathogen population. These ideas are consistent with detailed longitudinal studies of CTL responses in HIV-1 infected patients. For vaccine design, the model suggests that the major response should be directed against conserved epitopes even if they are subdominant. Nature Publishing Group 1995-06 Article NonPeerReviewed Nowak, M.A. <https://pure.iiasa.ac.at/view/iiasa/1481.html>, May, R.M., & Sigmund, K. <https://pure.iiasa.ac.at/view/iiasa/282.html> (1995). Antigenic oscillations and shifting immunodominance in HIV-1 infections. Nature 375 (6532) 606-611. 10.1038/375606a0 <https://doi.org/10.1038/375606a0>. 10.1038/375606a0 10.1038/375606a0 10.1038/375606a0 info:eu-repo/semantics/humanStartPage