Identification of epitopes targeted by TCR-MHC pairs

2020 Fiscal Year Annual Research Report

• Project/Area Number: 18H02430
• Research Institution: Osaka University
• Principal Investigator: Standley Daron 大阪大学, 微生物病研究所, 教授 (00448028)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: Adaptive immunity / T cell / epitope / machine learning; / structural modeling

Outline of Annual Research Achievements

We have achieved the main objective of this project: to develop a general method to predict the epitope targeted by a given T cell receptor (TCR) and major histocompatibility complex (MHC). To build a 3D model of each TCR sequence, we have developed Repertoire Builder, which can generate 10,000 antibody or TCR models in approximately 30 minutes more accurate than any other tested server (Schritt, D. et al. MSDE 2019). Next, to cluster the TCRs, we developed InterClone, which can cluster antibodies or TCRs into epitope-specific groups (Xu, Z. et al. MSDE 2019). Next, we can construct a 3D model of the TCR-epitope-MHC complex using ImmuneScape (Li, S. et al. Meth Mol Biol 2019). The final step in the pipeline is to develop a score that can distinguish true peptide epitopes from false ones. We have developed such a score and demonstrate that it dramatically out-performs the original ImmuneScape score. Using the above pipeline, we have made significant contributions to the identification of antigens involved in allergy (Takeda, K. et al. J Allergy Clin Immunol 2019), modeled antibodies involved in enhancing SARS-CoV-2 infection (Liu, Y. et al. Cell 2021), modeled CAR T cell receptors (Singh, N. et al Nat Med 2021) and modeled the self-reactive epitopes involved in neuromyelitis optica spectrum disorder (in prep). These tools are currently being applied to the identification of SARS-CoV-2 T cell epitopes in Japanese COVID-19 patients.

Research Progress Status

令和2年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

令和2年度が最終年度であるため、記入しない。

Research Products

• [Journal Article] An infectivity-enhancing site on the SARS-CoV-2 spike protein is targeted by COVID-19 patient antibodies (2021)
  • Author(s): Liu Yafei +21 +Standley Daron M.、Shioda Tatsuo、Arase Hisashi
  • Journal Title: Cell in press Volume: 1 Pages: 1-1
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Antigen-independent activation enhances the efficacy of 4-1BB-costimulated CD22 CAR T cells (2021)
  • Author(s): Nathan Singh + 26+ Daron M Standley +6 + Marco Ruella
  • Journal Title: Nat Med. in press Volume: 1 Pages: 1-1
• [Journal Article] Methods for sequence and structural analysis of B and T cell receptor repertoires (2020)
  • Author(s): Teraguchi Shunsuke、Saputri Dianita S.、Llamas-Covarrubias Mara Anais、Davila Ana、Diez Diego、Nazlica Sedat Aybars、Rozewicki John、Ismanto Hendra S.、Wilamowski Jan、Xie Jiaqi、Xu Zichang、Loza-Lopez Martin de Jesus、van Eerden Floris J.、Li Songling、Standley Daron M.
  • Journal Title: Computational and Structural Biotechnology Journal Volume: 18 Pages: 2000～2011
  • DOI: 10.1016/j.csbj.2020.07.008
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Analysis of Protein Intermolecular Interactions with MAFFT-DASH (2020)
  • Author(s): Rozewicki John、Li Songling、Katoh Kazutaka、Standley Daron M.
  • Journal Title: Methods Mol Biol 2231 Volume: 1 Pages: 163～177
  • DOI: 10.1007/978-1-0716-1036-7_11
• [Presentation] "Toward high-throughput antibody-antigen modeling" (2020)
  • Author(s): Daron Standley
  • Organizer: Kobe Univ. (The Basis for Computational Life Science 7)
  • Invited