Breaking tolerance with engineered class I antigen-presenting molecules
Abstract
Provision of sufficient activating signals can drive self-tolerant T cells to cross-react on self-peptide-MHC in a breakdown of tolerance. This approach has been applied in the development of heteroclitic peptide vaccines, which retain sufficient similarity to self to allow reactivation of effector cells on unaltered self-epitopes but require detailed knowledge about the behavior of individual altered self-peptide antigens. We designed altered-self MHC mutant antigen-presenting molecules to drive CTL capable of cross-reacting on self-peptide-MHC and demonstrate the breaking of self-tolerance to defined and undefined self-antigens. These findings bear particular importance in the field of cancer immunotherapy in which breaking tolerance to weakly antigenic cancer-associated antigens is fundamental to vaccination strategies.
- Publication:
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Proceedings of the National Academy of Science
- Pub Date:
- February 2019
- DOI:
- 10.1073/pnas.1807465116
- Bibcode:
- 2019PNAS..116.3136P