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Molecular properties of gp100‐reactive T‐cell receptors drive the cytokine profile and antitumor efficacy of transgenic host T cells
Author(s) -
Eby Jonathan M.,
Smith Angela R.,
Riley Timothy P.,
Cosgrove Cormac,
Ankney Christian M.,
Henning Steven W.,
Paulos Chrystal M.,
GarrettMayer Elizabeth,
Luiten Rosalie M.,
Nishimura Michael I.,
Baker Brian M.,
Le Poole I. Caroline
Publication year - 2019
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/pcmr.12724
Subject(s) - t cell receptor , streptamer , t cell , cd8 , biology , microbiology and biotechnology , cytotoxic t cell , receptor , adoptive cell transfer , context (archaeology) , antigen presenting cell , antigen , immunology , immune system , in vitro , biochemistry , paleontology
To study the contribution of T‐cell receptors ( TCR ) to resulting T‐cell responses, we studied three different human αβ TCR s, reactive to the same gp100‐derived peptide presented in the context of HLA ‐A*0201. When expressed in primary CD 8 T cells, all receptors elicited classic antigen‐induced IFN ‐γ responses, which correlated with TCR affinity for peptide– MHC in the order T4H2 > R6C12 > SIL v44. However, SIL v44 elicited superior IL ‐17A release. Importantly, in vivo, SIL v44‐transgenic T cells mediated superior antitumor responses to 888‐A2 + human melanoma tumor cells upon adoptive transfer into tumor‐challenged mice while maintaining IL ‐17 expression. Modeling of the TCR ternary complexes suggested architectural differences between SIL v44 and the other complexes, providing a potential structural basis for the observed differences. Overall, the data reveal a more prominent role for the T‐cell receptor in defining host T‐cell physiology than traditionally assumed, while parameters beyond IFN ‐γ secretion and TCR affinity ultimately determine the reactivity of tumor‐reactive T cells.