6MNO

6235 TCR bound to I-Ab Padi4

Summary for 6MNO

• Entry DOI: 10.2210/pdb6mno/pdb
• Descriptor: H-2 class II histocompatibility antigen, A-B alpha chain, Padi4 (92-105) peptide and MHC Class II I-Ab beta chain, 6235 TCR alpha chain, ... (4 entities in total)
• Functional Keywords: t cell receptor, major histocompatibility complex, immune system
• Biological source: Mus musculus (Mouse); More
• Total number of polymer chains: 4
• Total formula weight: 95271.77

Authors

Stadinski, B.D.,Blevins, S.J.,Huseby, E.S. (deposition date: 2018-10-02, release date: 2019-07-03, Last modification date: 2024-10-16)

Primary citation

Stadinski, B.D.,Blevins, S.J.,Spidale, N.A.,Duke, B.R.,Huseby, P.G.,Stern, L.J.,Huseby, E.S.
A temporal thymic selection switch and ligand binding kinetics constrain neonatal Foxp3+Tregcell development.
Nat.Immunol., 20:1046-1058, 2019

PubMed Abstract: The neonatal thymus generates Foxp3 regulatory T (tT) cells that are critical in controlling immune homeostasis and preventing multiorgan autoimmunity. The role of antigen specificity on neonatal tT cell selection is unresolved. Here we identify 17 self-peptides recognized by neonatal tT cells, and reveal ligand specificity patterns that include self-antigens presented in an age- and inflammation-dependent manner. Fate-mapping studies of neonatal peptidyl arginine deiminase type IV (Padi4)-specific thymocytes reveal disparate fate choices. Neonatal thymocytes expressing T cell receptors that engage IA-Padi4 with moderate dwell times within a conventional docking orientation are exported as tT cells. In contrast, Padi4-specific T cell receptors with short dwell times are expressed on CD4 T cells, while long dwell times induce negative selection. Temporally, Padi4-specific thymocytes are subject to a developmental stage-specific change in negative selection, which precludes tT cell development. Thus, a temporal switch in negative selection and ligand binding kinetics constrains the neonatal tT selection window.

PubMed: 31209405
DOI: 10.1038/s41590-019-0414-1

Experimental method

X-RAY DIFFRACTION (2.9 Å)