Antigenic oscillations and shifting immunodominance in HIV-1 infections

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.

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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.

Item Type: Article
Research Programs: Adaptive Dynamics Network (ADN)
Bibliographic Reference: Nature; 375(6532):606-611 (15 June 1995)
Depositing User: IIASA Import
Date Deposited: 15 Jan 2016 02:05
Last Modified: 27 Aug 2021 17:35

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