MHC class I-restricted epitope spreading in the context of tumor rejection following vaccination with a single immunodominant CTL epitope
✍ Scribed by Khaled el-Shami; Boaz Tirosh; Erez Bar-Haim; Lior Carmon; Ezra Vadai; Mati Fridkin; Michael Feldman; Lea Eisenbach
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 132 KB
- Volume
- 29
- Category
- Article
- ISSN
- 0014-2980
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✦ Synopsis
Epitope spreading is a process whereby epitopes distinct from and non-cross-reactive with an inducing epitope become targets of an evolving immune response. This phenomenon has been associated most notably with the progression of naturally occurring or experimentally induced chronic autoimmune diseases. We have investigated the potential occurrence of epitope spreading in the context of antitumor cytotoxic T cell (CTL) responses using chicken ovalbumin (OVA) as a model antigen. Our results indicate that following rejection of OVAexpressing EG.7 tumor cells effectuated by a CTL response which is induced against the MHC class I-restricted immunodominant epitope OVA257-264, there occurs intramolecular diversification of the CTL response to two additional OVA-derived epitopes, OVA176-183 and OVA55-62, as well as intermolecular spreading to other endogenous tumor-derived determinants. It seems that CTL-mediated tumor cell destruction in vivo favors crosspresentation of additional epitopes with the consequent activation of additional tumorreactive lymphocytes. The process of epitope spreading in that context has obvious important implications for the design of antigen-specific antitumor immunotherapies.