Parsing digital or analogue TCR performance through piconewton forces.

التفاصيل البيبلوغرافية
العنوان: Parsing digital or analogue TCR performance through piconewton forces.
المؤلفون: Akitsu A, Kobayashi E, Feng Y, Stephens HM, Brazin KN, Masi DJ, Kirpatrick EH, Mallis RJ, Duke-Cohan JS, Booker MA, Cinella V, Feng WW, Holliday EL, Lee JJ, Zienkiewicz KJ, Tolstorukov MY, Hwang W, Lang MJ, Reinherz EL
المصدر: BioRxiv : the preprint server for biology [bioRxiv] 2023 Nov 30. Date of Electronic Publication: 2023 Nov 30.
نوع المنشور: Preprint
اللغة: English
بيانات الدورية: Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet ISSN: 2692-8205 (Electronic) Linking ISSN: 26928205 NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE
مستخلص: αβ T-cell receptors (TCRs) 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 upregulation in vitro . Given neoantigen array paucity, digital TCRs are likely critical for immunotherapies.
One Sentence Summary: Quality of ligand recognition in a T-cell repertoire is revealed through application of physical load on clonal T-cell receptor (TCR)-pMHC bonds.
التعليقات: Update in: Sci Adv. 2024 Aug 16;10(33):eado4313. doi: 10.1126/sciadv.ado4313. (PMID: 39141734)
معلومات مُعتمدة: P01 AI143565 United States AI NIAID NIH HHS
تواريخ الأحداث: Date Created: 20231211 Latest Revision: 20240820
رمز التحديث: 20240820
مُعرف محوري في PubMed: PMC10705438
DOI: 10.1101/2023.11.29.568292
PMID: 38076892
قاعدة البيانات: MEDLINE
الوصف
تدمد:2692-8205
DOI:10.1101/2023.11.29.568292