       Document 0364
 DOCN  M9620364
 TI    Immune responses against multiple epitopes.
 DT    9602
 AU    Nowak MA; May RM; Sigmund K; Department of Zoology, University of
       Oxford, U.K.
 SO    J Theor Biol. 1995 Aug 7;175(3):325-53. Unique Identifier : AIDSLINE
       MED/96030939
 AB    The current understanding of antigenic escape dynamics is based on
       models with single epitopes. The usual idea is that a mutation which
       enables a pathogen (virus, bacteria, etc) to escape from a given immune
       response confers a selective advantage. The escape mutant may then
       increase in abundance until it induces a new specific response against
       itself. In this paper a new picture is developed, based on mathematical
       models of immune responses against several epitopes; the simplest such
       models can have very complicated dynamics, with some surprising
       features. The emergence of an escape mutant can shift the immunodominant
       response to another epitope. Even in the absence of mutations, antigenic
       oscillation is found, with distinct peaks of different virus variants
       and fluctuations in the size and specificity of the immune responses.
       The model also provides a general theory for immunodominance in the
       presence of antigenic variation. Immunodominance is determined by the
       immunogenicity and by the antigenic diversity of the competing epitopes.
       Antigenic oscillations and fluctuations in the cytotoxic T-lymphocyte
       response have been observed in infections with the human
       immunodeficiency virus (HIV). Shifting the immune responses to weaker
       epitopes can represent a mechanism for disease progression based on
       evolutionary dynamics and antigenic diversity of the virus.
 DE    Antigenic Variation  *Epitopes  Human  *Immunity, Cellular
       Immunodominant Epitopes  Immunotherapy  Mathematics  *Models,
       Immunological  Support, Non-U.S. Gov't  T-Lymphocytes,
       Cytotoxic/IMMUNOLOGY  Virus Diseases/*IMMUNOLOGY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

