eprintid: 4236 rev_number: 7 eprint_status: archive userid: 351 dir: disk0/00/00/42/36 datestamp: 2016-01-15 02:05:02 lastmod: 2021-08-27 17:35:54 status_changed: 2016-01-15 02:05:02 type: article metadata_visibility: show item_issues_count: 1 creators_name: Nowak, M.A. creators_name: May, R.M. creators_name: Sigmund, K. creators_id: 7540 creators_id: 1050 title: Antigenic oscillations and shifting immunodominance in HIV-1 infections ispublished: pub internal_subjects: iis_bio internal_subjects: iis_ecl internal_subjects: iis_mod internal_subjects: iis_met divisions: prog_adn abstract: 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. date: 1995-06 date_type: published publisher: Nature Publishing Group id_number: 10.1038/375606a0 iiasapubid: XJ-95-103 iiasa_bibref: Nature; 375(6532):606-611 (15 June 1995) iiasa_bibnotes: [doi:10.1038/375606a0] (Letter) creators_browse_id: 1481 creators_browse_id: 282 full_text_status: none publication: Nature volume: 375 number: 6532 pagerange: 606-611 refereed: FALSE issn: 0028-0836 coversheets_dirty: FALSE fp7_type: info:eu-repo/semantics/article citation: Nowak, M.A. , May, R.M., & Sigmund, K. (1995). Antigenic oscillations and shifting immunodominance in HIV-1 infections. Nature 375 (6532) 606-611. 10.1038/375606a0 .