Parsing digital or analog TCR performance through piconewton forces-Reference-Cited by-同舟云学术

Parsing digital or analog TCR performance through piconewton forces

Published:2024-08-16 Issue:33 Volume:10 Page:
ISSN:2375-2548
Container-title:Science Advances
language:en
Short-container-title:Sci. Adv.

Author:

Akitsu Aoi¹²³^ORCID,Kobayashi Eiji¹²³^ORCID,Feng Yinnian⁴,Stephens Hannah M.⁴^ORCID,Brazin Kristine N.¹²³^ORCID,Masi Daniel J.⁴,Kirkpatrick Evan H.⁴^ORCID,Mallis Robert J.¹²³⁵^ORCID,Duke-Cohan Jonathan S.¹²³^ORCID,Booker Matthew A.⁶^ORCID,Cinella Vincenzo¹²^ORCID,Feng William W.²³^ORCID,Holliday Elizabeth L.⁴^ORCID,Lee Jonathan J.¹²^ORCID,Zienkiewicz Katarzyna J.⁴,Tolstorukov Michael Y.⁶^ORCID,Hwang Wonmuk⁷^ORCID,Lang Matthew J.⁴⁸^ORCID,Reinherz Ellis L.¹²³^ORCID

Affiliation:

1. Laboratory of Immunobiology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.

2. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.

3. Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.

4. Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN 37212, USA.

5. Department of Dermatology, Harvard Medical School, Boston, MA 02115, USA.

6. Department of Informatics and Analytics, Dana-Farber Cancer Institute, Boston, MA 02115, USA.

7. Departments of Biomedical Engineering, Materials Science and Engineering, Physics and Astronomy, Texas A&M University, College Station, TX 77843, USA.

8. Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.

Abstract

αβ T cell receptors (TCRs) principally recognize aberrant peptides bound to major histocompatibility complex molecules (pMHCs) on unhealthy cells, amplifying specificity and sensitivity through physical load placed on the TCR-pMHC bond during immunosurveillance. To understand this mechanobiology, TCRs stimulated by abundantly and sparsely arrayed epitopes (NP 366–374 /D b and PA 224–233 /D b , respectively) following in vivo influenza A virus infection were studied with optical tweezers. While certain NP repertoire CD8 T lymphocytes require many ligands for activation, others are digital, needing just few. Conversely, all PA TCRs perform digitally, exhibiting pronounced bond lifetime increases through sustained, energizing volleys of structural transitioning. Optimal digital performance is superior in vivo, correlating with ERK phosphorylation, CD3 loss, and activation marker up-regulation in vitro. Given neoantigen array paucity, digital TCRs are likely critical for immunotherapies.

Publisher

American Association for the Advancement of Science (AAAS)

Link

https://www.science.org/doi/pdf/10.1126/sciadv.ado4313

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