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A luminescence-based method to assess antigen presentation and antigen-specific T cell responses for in vitro screening of immunomodulatory checkpoints and therapeutics.
Álvarez Freile, Jimena; Qi, Yuzhu; Jacob, Lisa; Lobo, Maria Franceskin; Lourens, Harm Jan; Huls, Gerwin; Bremer, Edwin.
Afiliación
  • Álvarez Freile J; Department of Hematology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
  • Qi Y; Department of Hematology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
  • Jacob L; Department of Hematology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
  • Lobo MF; Department of Hematology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
  • Lourens HJ; Department of Hematology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
  • Huls G; Department of Hematology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
  • Bremer E; Department of Hematology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Front Immunol ; 14: 1233113, 2023.
Article en En | MEDLINE | ID: mdl-37559730
Investigations into the strength of antigen-specific responses in vitro is becoming increasingly relevant for decision making in early-phase research of novel immunotherapeutic approaches, including adoptive cell but also immune checkpoint inhibitor (ICI)-based therapies. In the latter, antigen-specific rapid and high throughput tools to investigate MHC/antigen-specific T cell receptor (TCR) activation haven't been implemented yet. Here, we present a simple and rapid luminescence-based approach using the human papillomavirus 16 (HPV16) E711-20 peptide as model antigen and E7-TCR transgenic Jurkat.NFAT-luciferase reporter cells. Upon E7 peptide pulsing of HLA-A2+ cell lines and macrophages, an effector to target ratio dependent increase in luminescence compared to non-pulsed cells was observed after co-incubation with E7-TCR expressing Jurkat, but not with parental cells. Analogous experiments with cells expressing full-length HPV16 identified that E7-specific activation of Jurkat cells enabled detection of endogenous antigen processing and MHC-I presentation. As proof of concept, overexpression of established checkpoints/inhibitory molecules (e.g., PD-L1 or HLA-G) significantly reduced the E7-specific TCR-induced luminescence, an effect that could be restored after treatment with corresponding targeting antagonistic antibodies. Altogether, the luminescence-based method described here represents an alternative approach for the rapid evaluation of MHC-dependent antigen-specific T cell responses in vitro. It can be used as a rapid tool to evaluate the impact of the immunosuppressive tumor microenvironment or novel ICI in triggering effective T cell responses, as well as speeding up the development of novel therapeutics within the immune-oncology field.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Presentación de Antígeno / Luminiscencia Tipo de estudio: Diagnostic_studies / Prognostic_studies / Screening_studies Límite: Humans Idioma: En Revista: Front Immunol Año: 2023 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Suiza
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Presentación de Antígeno / Luminiscencia Tipo de estudio: Diagnostic_studies / Prognostic_studies / Screening_studies Límite: Humans Idioma: En Revista: Front Immunol Año: 2023 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Suiza