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Large libraries of single-chain trimer peptide-MHCs enable antigen-specific CD8+ T cell discovery and analysis.
Chour, William; Choi, Jongchan; Xie, Jingyi; Chaffee, Mary E; Schmitt, Thomas M; Finton, Kathryn; DeLucia, Diana C; Xu, Alexander M; Su, Yapeng; Chen, Daniel G; Zhang, Rongyu; Yuan, Dan; Hong, Sunga; Ng, Alphonsus H C; Butler, Jonah Z; Edmark, Rick A; Jones, Lesley C; Murray, Kim M; Peng, Songming; Li, Guideng; Strong, Roland K; Lee, John K; Goldman, Jason D; Greenberg, Philip D; Heath, James R.
Afiliación
  • Chour W; Institute for Systems Biology, Seattle, WA, 98109, USA.
  • Choi J; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, 91125, USA.
  • Xie J; Institute for Systems Biology, Seattle, WA, 98109, USA.
  • Chaffee ME; Institute for Systems Biology, Seattle, WA, 98109, USA.
  • Schmitt TM; Molecular Engineering & Sciences Institute, University of Washington, Seattle, WA, 98195, USA.
  • Finton K; Program in Immunology, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA.
  • DeLucia DC; Program in Immunology, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA.
  • Xu AM; Program in Immunology, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA.
  • Su Y; Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA.
  • Chen DG; Institute for Systems Biology, Seattle, WA, 98109, USA.
  • Zhang R; Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA, 91125, USA.
  • Yuan D; Institute for Systems Biology, Seattle, WA, 98109, USA.
  • Hong S; Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA, 91125, USA.
  • Ng AHC; Institute for Systems Biology, Seattle, WA, 98109, USA.
  • Butler JZ; Department of Microbiology and Department of Informatics, University of Washington, Seattle, WA, 98195, USA.
  • Edmark RA; Institute for Systems Biology, Seattle, WA, 98109, USA.
  • Jones LC; Department of Bioengineering, University of Washington, Seattle, WA, 98195, USA.
  • Murray KM; Institute for Systems Biology, Seattle, WA, 98109, USA.
  • Peng S; Department of Bioengineering, University of Washington, Seattle, WA, 98195, USA.
  • Li G; Institute for Systems Biology, Seattle, WA, 98109, USA.
  • Strong RK; Institute for Systems Biology, Seattle, WA, 98109, USA.
  • Lee JK; Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA, 91125, USA.
  • Goldman JD; Program in Immunology, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA.
  • Greenberg PD; Institute for Systems Biology, Seattle, WA, 98109, USA.
  • Heath JR; Institute for Systems Biology, Seattle, WA, 98109, USA.
Commun Biol ; 6(1): 528, 2023 05 16.
Article en En | MEDLINE | ID: mdl-37193826
The discovery and characterization of antigen-specific CD8+ T cell clonotypes typically involves the labor-intensive synthesis and construction of peptide-MHC tetramers. We adapt single-chain trimer (SCT) technologies into a high throughput platform for pMHC library generation, showing that hundreds can be rapidly prepared across multiple Class I HLA alleles. We use this platform to explore the impact of peptide and SCT template mutations on protein expression yield, thermal stability, and functionality. SCT libraries were an efficient tool for identifying T cells recognizing commonly reported viral epitopes. We then construct SCT libraries to capture SARS-CoV-2 specific CD8+ T cells from COVID-19 participants and healthy donors. The immunogenicity of these epitopes is validated by functional assays of T cells with cloned TCRs captured using SCT libraries. These technologies should enable the rapid analyses of peptide-based T cell responses across several contexts, including autoimmunity, cancer, or infectious disease.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos T CD8-positivos / COVID-19 Límite: Humans Idioma: En Revista: Commun Biol Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
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PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos T CD8-positivos / COVID-19 Límite: Humans Idioma: En Revista: Commun Biol Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido