Details

Autor(en) / Beteiligte

• Grace, Beth E.
• Backlund, Coralie M.
• Morgan, Duncan M.
• Kang, Byong H.
• Singh, Nishant K.
• Huisman, Brooke D.
• Rappazzo, C. Garrett
• Moynihan, Kelly D.
• Maiorino, Laura
• Dobson, Connor S.
• Kyung, Taeyoon
• Gordon, Khloe S.
• Holec, Patrick V.
• Mbah, Overbeck C. Takou
• Garafola, Daniel
• Wu, Shengwei
• Love, J. Christopher
• Wittrup, K. Dane
• Irvine, Darrell J.
• Birnbaum, Michael E.

Titel

Identification of Highly Cross-Reactive Mimotopes for a Public T Cell Response in Murine Melanoma

Ist Teil von

• Frontiers in immunology, 2022-06, Vol.13, p.886683-886683

Ort / Verlag

Frontiers Media S.A

Erscheinungsjahr

2022

Link zum Volltext

Quelle

Electronic Journals Library

Beschreibungen/Notizen

• 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 + 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 in vivo , engineered antigen mimotopes induced a significant expansion of CD8 + T cells cross-reactive to the original antigen. Vaccination with mimotopes resulted in killing of antigen-loaded cells in vivo 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.