@article{iiasa4236,
          volume = {375},
          number = {6532},
           month = {June},
           title = {Antigenic oscillations and shifting immunodominance in HIV-1 infections},
       publisher = {Nature Publishing Group},
            year = {1995},
         journal = {Nature},
             doi = {10.1038/375606a0},
           pages = {606--611},
             url = {https://pure.iiasa.ac.at/id/eprint/4236/},
            issn = {0028-0836},
        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.},
          author = {Nowak, M. A. and May, R. M. and Sigmund, K.}
}