Pre-T cell receptors topologically sample self-ligands during thymocyte β-selection.
Journal
Science (New York, N.Y.)
ISSN: 1095-9203
Titre abrégé: Science
Pays: United States
ID NLM: 0404511
Informations de publication
Date de publication:
08 01 2021
08 01 2021
Historique:
received:
30
07
2020
accepted:
03
12
2020
pubmed:
19
12
2020
medline:
17
2
2021
entrez:
18
12
2020
Statut:
ppublish
Résumé
Self-discrimination, a critical but ill-defined molecular process programmed during thymocyte development, requires myriad pre-T cell receptors (preTCRs) and αβTCRs. Using x-ray crystallography, we show how a preTCR applies the concave β-sheet surface of its single variable domain (Vβ) to "horizontally" grab the protruding MHC α2-helix. By contrast, αβTCRs purpose all six complementarity-determining region (CDR) loops of their paired VαVβ module to recognize peptides bound to major histocompatibility complex molecules (pMHCs) in "vertical" head-to-head binding. The preTCR topological fit ensures that CDR3β reaches the peptide's featured C-terminal segment for pMHC sampling, establishing the subsequent αβTCR canonical docking mode. "Horizontal" docking precludes germline CDR1β- and CDR2β-MHC binding to broaden β-chain repertoire diversification before αβTCR-mediated selection refinement. Thus, one subunit successively attunes the recognition logic of related multicomponent receptors.
Identifiants
pubmed: 33335016
pii: science.abe0918
doi: 10.1126/science.abe0918
pmc: PMC8011828
mid: NIHMS1681834
doi:
Substances chimiques
Ligands
0
Receptors, Antigen, T-Cell, alpha-beta
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
181-185Subventions
Organisme : NHLBI NIH HHS
ID : T32 HL066987
Pays : United States
Organisme : NIBIB NIH HHS
ID : P41 EB002026
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI037581
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI143565
Pays : United States
Organisme : NIH HHS
ID : S10 OD028526
Pays : United States
Organisme : NIGMS NIH HHS
ID : P01 GM047467
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI136960
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI136301
Pays : United States
Organisme : NIH HHS
ID : S10 OD023513
Pays : United States
Informations de copyright
Copyright © 2021, American Association for the Advancement of Science.
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