RT Journal Article
SR 00
ID 10.1038/375606a0
A1 Nowak, M.A.
A1 May, R.M.
A1 Sigmund, K.
T1 Antigenic oscillations and shifting immunodominance in HIV-1 infections
JF Nature
YR 1995
FD 1995-06
VO 375
IS 6532
SP 606
OP 611
AB 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.
PB Nature Publishing Group
SN 0028-0836
LK https://pure.iiasa.ac.at/id/eprint/4236/