| dc.creator |
Grace, Beth E. |
|
| dc.creator |
Backlund, Coralie M. |
|
| dc.creator |
Morgan, Duncan M. |
|
| dc.creator |
Kang, Byong H. |
|
| dc.creator |
Singh, Nishant K. |
|
| dc.creator |
Huisman, Brooke D. |
|
| dc.creator |
Rappazzo, C. Garrett |
|
| dc.creator |
Moynihan, Kelly D. |
|
| dc.creator |
Maiorino, Laura |
|
| dc.creator |
Dobson, Connor S. |
|
| dc.creator |
Kyung, Taeyoon |
|
| dc.creator |
Gordon, Khloe S. |
|
| dc.creator |
Holec, Patrick V. |
|
| dc.creator |
Mbah, Overbeck C. Takou |
|
| dc.creator |
Garafola, Daniel |
|
| dc.creator |
Wu, Shengwei |
|
| dc.creator |
Love, J. Christopher |
|
| dc.creator |
Wittrup, K. Dane |
|
| dc.creator |
Irvine, Darrell J. |
|
| dc.creator |
Birnbaum, Michael E. |
|
| dc.date |
2022-07-11T18:11:14Z |
|
| dc.date |
2022-07-11T18:11:14Z |
|
| dc.date |
2022-06-23 |
|
| dc.date.accessioned |
2023-02-17T20:09:14Z |
|
| dc.date.available |
2023-02-17T20:09:14Z |
|
| dc.identifier |
1664-3224 |
|
| dc.identifier |
https://hdl.handle.net/1721.1/143653 |
|
| dc.identifier |
Grace, Beth E., Backlund, Coralie M., Morgan, Duncan M., Kang, Byong H., Singh, Nishant K. et al. 2022. "Identification of Highly Cross-Reactive Mimotopes for a Public T Cell Response in Murine Melanoma." Frontiers in Immunology, 13. |
|
| dc.identifier.uri |
http://localhost:8080/xmlui/handle/CUHPOERS/242134 |
|
| dc.description |
<jats:p>While immune checkpoint blockade results in durable responses for some patients, many others have not experienced such benefits. These treatments rely upon reinvigorating specific T cell-antigen interactions. However, it is often unknown what antigens are being recognized by T cells or how to potently induce antigen-specific responses in a broadly applicable manner. Here, we characterized the CD8<jats:sup>+</jats:sup> T cell response to a murine model of melanoma following combination immunotherapy to determine the basis of tumor recognition. Sequencing of tumor-infiltrating T cells revealed a repertoire of highly homologous TCR sequences that were particularly expanded in treated mice and which recognized an antigen from an endogenous retrovirus. While vaccination against this peptide failed to raise a protective T cell response <jats:italic>in vivo</jats:italic>, engineered antigen mimotopes induced a significant expansion of CD8<jats:sup>+</jats:sup> T cells cross-reactive to the original antigen. Vaccination with mimotopes resulted in killing of antigen-loaded cells <jats:italic>in vivo</jats:italic> yet showed modest survival benefit in a prophylactic vaccine paradigm. Together, this work demonstrates the identification of a dominant tumor-associated antigen and generation of mimotopes which can induce robust functional T cell responses that are cross-reactive to the endogenous antigen across multiple individuals.</jats:p> |
|
| dc.format |
application/pdf |
|
| dc.publisher |
Frontiers Media SA |
|
| dc.relation |
10.3389/fimmu.2022.886683 |
|
| dc.relation |
Frontiers in Immunology |
|
| dc.rights |
Creative Commons Attribution 4.0 International license |
|
| dc.rights |
https://creativecommons.org/licenses/by/4.0/ |
|
| dc.source |
Frontiers |
|
| dc.title |
Identification of Highly Cross-Reactive Mimotopes for a Public T Cell Response in Murine Melanoma |
|
| dc.type |
Article |
|
| dc.type |
http://purl.org/eprint/type/JournalArticle |
|