A biomimetic five-module chimeric antigen receptor ( 5M CAR) designed to target and eliminate antigen-specific T cells

• DOI: 10.1073/pnas.2012495117
• Publication Date: 2020-11-03T01:32:04Z
• Authors: Shio Kobayashi; Martin A. Thelin; Heather L. Parrish; Neha R. Deshpande; Mark S. Lee; Alborz Karimzadeh; Monika A. Niewczas; Thomas Serwold; Michael S. Kuhns
• Keywords: CTL*; Streptamer

T cells express clonotypic cell receptors (TCRs) that recognize peptide antigens in the context of class I or II MHC molecules (pMHCI/II). These receptor modules associate with three signaling (CD3γε, δε, and ζζ) work concert a coreceptor module (either CD8 CD4) to drive activation response pMHCI/II. Here, we describe first-generation biomimetic five-module chimeric antigen (5MCAR). We show 1) built ectodomains pMHCII assemble CD3 into complexes redirect cytotoxic lymphocyte (CTL) specificity function TCRs pMHCII-specific CD4+ cells, 2) surrogate enhance these complexes. Furthermore, demonstrate adoptively transferred 5MCAR-CTLs can mitigate type diabetes by targeting autoimmune NOD mice. This provides framework for construction 5MCARs be used as tools study impact particular antigen-specific immune responses, may hold potential ameliorating diseases mediated pathogenic cells.