TY  - JOUR
ID  - iiasa4236
UR  - https://pure.iiasa.ac.at/id/eprint/4236/
IS  - 6532
A1  - Nowak, M.A.
A1  - May, R.M.
A1  - Sigmund, K.
Y1  - 1995/06//
N2  - 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
JF  - Nature
VL  - 375
SN  - 0028-0836
TI  - Antigenic oscillations and shifting immunodominance in HIV-1 infections
SP  - 606
AV  - none
EP  - 611
ER  -