IIASA RepositoryAntigenic oscillations and shifting immunodominance in HIV-1 infectionsM.A.NowakauthorR.M.MayauthorK.SigmundauthorAtypical 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.1995-06Nature Publishing GroupArticle

For work being deposited by its own author: In self-archiving this collection of files and associated bibliographic metadata, I grant IIASA Repository the right to store them and to make them permanently available publicly for free on-line. I declare that this material is my own intellectual property and I understand that IIASA Repository does not assume any responsibility if there is any breach of copyright in distributing these files or metadata. (All authors are urged to prominently assert their copyright on the title page of their work.)

For work being deposited by someone other than its author: I hereby declare that the collection of files and associated bibliographic metadata that I am archiving at IIASA Repository) is in the public domain. If this is not the case, I accept full responsibility for any breach of copyright that distributing these files or metadata may entail.

Clicking on the deposit button indicates your agreement to these terms.