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@ARTICLE{Meyer:287071,
      author       = {M. Meyer$^*$ and C. Parpoulas$^*$ and T. Barthélémy$^*$
                      and J. P. Becker$^*$ and P. Charoentong$^*$ and Y. Lyu$^*$
                      and S. Börsig$^*$ and N. Bulbuc$^*$ and C. Tessmer$^*$ and
                      L. Weinacht$^*$ and D. Ibberson and P. Schmidt$^*$ and R.
                      Pipkorn$^*$ and S. B. Eichmüller$^*$ and P. Steinberger and
                      K. Lindner$^*$ and I. Poschke$^*$ and M. Platten$^*$ and S.
                      Fröhling$^*$ and A. B. Riemer$^*$ and J. C. Hassel and M.
                      P. Roberti$^*$ and D. Jäger$^*$ and I. Zörnig$^*$ and F.
                      Momburg$^*$},
      title        = {{M}edi{M}er: a versatile do-it-yourself peptide-receptive
                      {MHC} class {I} multimer platform for tumor
                      neoantigen-specific {T} cell detection.},
      journal      = {Frontiers in immunology},
      volume       = {14},
      issn         = {1664-3224},
      address      = {Lausanne},
      publisher    = {Frontiers Media},
      reportid     = {DKFZ-2024-00164},
      pages        = {1294565},
      year         = {2023},
      note         = {#EA:D121#EA:D120#LA:D120# / HI-TRON / Front Immunol. 2023;
                      14: 1294565.Published online 2024 Jan 4. doi:
                      10.3389/fimmu.2023.1294565 / in 2023 mitgezählt},
      abstract     = {Peptide-loaded MHC class I (pMHC-I) multimers have
                      revolutionized our capabilities to monitor
                      disease-associated T cell responses with high sensitivity
                      and specificity. To improve the discovery of T cell
                      receptors (TCR) targeting neoantigens of individual tumor
                      patients with recombinant MHC molecules, we developed a
                      peptide-loadable MHC class I platform termed MediMer.
                      MediMers are based on soluble disulfide-stabilized
                      β2-microglobulin/heavy chain ectodomain single-chain dimers
                      (dsSCD) that can be easily produced in large quantities in
                      eukaryotic cells and tailored to individual patients' HLA
                      allotypes with only little hands-on time. Upon transient
                      expression in CHO-S cells together with ER-targeted BirA
                      biotin ligase, biotinylated dsSCD are purified from the cell
                      supernatant and are ready to use. We show that CHO-produced
                      dsSCD are free of endogenous peptide ligands. Empty dsSCD
                      from more than 30 different HLA-A,B,C allotypes, that were
                      produced and validated so far, can be loaded with synthetic
                      peptides matching the known binding criteria of the
                      respective allotypes, and stored at low temperature without
                      loss of binding activity. We demonstrate the usability of
                      peptide-loaded dsSCD multimers for the detection of human
                      antigen-specific T cells with comparable sensitivities as
                      multimers generated with peptide-tethered β2m-HLA heavy
                      chain single-chain trimers (SCT) and wild-type peptide-MHC-I
                      complexes prior formed in small-scale refolding reactions.
                      Using allotype-specific, fluorophore-labeled competitor
                      peptides, we present a novel dsSCD-based peptide binding
                      assay capable of interrogating large libraries of in silico
                      predicted neoepitope peptides by flow cytometry in a
                      high-throughput and rapid format. We discovered rare T cell
                      populations with specificity for tumor neoepitopes and
                      epitopes from shared tumor-associated antigens in peripheral
                      blood of a melanoma patient including a so far unreported
                      HLA-C*08:02-restricted NY-ESO-1-specific CD8+ T cell
                      population. Two representative TCR of this T cell
                      population, which could be of potential value for a broader
                      spectrum of patients, were identified by dsSCD-guided
                      single-cell sequencing and were validated by cognate pMHC-I
                      multimer staining and functional responses to autologous
                      peptide-pulsed antigen presenting cells. By deploying the
                      technically accessible dsSCD MHC-I MediMer platform, we hope
                      to significantly improve success rates for the discovery of
                      personalized neoepitope-specific TCR in the future by being
                      able to also cover rare HLA allotypes.},
      keywords     = {T cell receptor discovery (Other) / T cells (Other) /
                      neoepitope screening (Other) / peptide-MHC class I multimer
                      (Other) / personalized medicine (Other) / tumor
                      immunotherapy (Other) / tumor neoantigen (Other)},
      cin          = {D121 / D120 / D410 / D210 / D170 / HD01 / B340},
      ddc          = {610},
      cid          = {I:(DE-He78)D121-20160331 / I:(DE-He78)D120-20160331 /
                      I:(DE-He78)D410-20160331 / I:(DE-He78)D210-20160331 /
                      I:(DE-He78)D170-20160331 / I:(DE-He78)HD01-20160331 /
                      I:(DE-He78)B340-20160331},
      pnm          = {314 - Immunologie und Krebs (POF4-314)},
      pid          = {G:(DE-HGF)POF4-314},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:38239352},
      pmc          = {pmc:PMC10794645},
      doi          = {10.3389/fimmu.2023.1294565},
      url          = {https://inrepo02.dkfz.de/record/287071},
}