Document 1123
 DOCN  M9591123
 TI    Antigenic oscillations and shifting immunodominance in HIV-1 infections
       [see comments]
 DT    9509
 AU    Nowak MA; May RM; Phillips RE; Rowland-Jones S; Lalloo DG; McAdam S;
       Klenerman P; Koppe B; Sigmund K; Bangham CR; et al; Department of
       Zoology, University of Oxford, UK.
 SO    Nature. 1995 Jun 15;375(6532):606-11. Unique Identifier : AIDSLINE
       MED/95312083
 CM    Comment in: Nature 1995 Jun 15;375(6532):534
 AB    A typical 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 (ref. 11) 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 immunological 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.
 DE    Amino Acid Sequence  *Antigenic Variation  Cells, Cultured  CD4-Positive
       T-Lymphocytes/IMMUNOLOGY  Hemophilia/COMPLICATIONS/IMMUNOLOGY  Human
       HIV Antigens/*IMMUNOLOGY  HIV Infections/COMPLICATIONS/*IMMUNOLOGY
       HIV-1/*IMMUNOLOGY  HLA-B27 Antigen/IMMUNOLOGY  HLA-B8 Antigen/IMMUNOLOGY
       Immunodominant Epitopes/*IMMUNOLOGY  Models, Immunological  Molecular
       Sequence Data  Support, Non-U.S. Gov't  T-Lymphocytes,
       Cytotoxic/*IMMUNOLOGY  JOURNAL ARTICLE

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