"4236","7","archive","351",,,"disk0/00/00/42/36","2016-01-15 02:05:02","2021-08-27 17:35:54","2016-01-15 02:05:02","article",,,"show","","","1",,,"Nowak","M.A.","","","7540","","",,,,,"","","Antigenic oscillations and shifting immunodominance in HIV-1 infections","pub","","iis_bio","prog_adn",,,"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.","1995-06","published","Nature Publishing Group","10.1038/375606a0",,,,,,"",,,,,"",,,,,"",,,,,"","",,"","XJ-95-103","Nature; 375(6532):606-611 (15 June 1995)","[doi:10.1038/375606a0] (Letter)",,,,"1481","none",,,,"Nature","375","6532",,"606-611",,,,,,,,,,,"FALSE",,"0028-0836",,,,,,"","","","",,"","",,,,,,,"",,,,,"FALSE",,,"info:eu-repo/semantics/article",
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