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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).