6DIG

Crystal structure of DQA1*01:02/DQB1*06:02 in complex with a hypocretin peptide

Summary for 6DIG

• Entry DOI: 10.2210/pdb6dig/pdb
• Descriptor: MHC class II HLA-DQ-alpha chain, HLA class II histocompatibility antigen, DQ beta 1 chain, 13-mer peptide: ALA-GLY-ASN-HIS-ALA-ALA-GLY-ILE-LEU-THR-LEU-GLY-LYS, ... (7 entities in total)
• Functional Keywords: mhc class ii hla, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 49810.37

Authors

Birtley, J.R.,Stern, L.J.,Mellins, E.D.,Jiang, W. (deposition date: 2018-05-23, release date: 2019-05-08, Last modification date: 2024-11-13)

Primary citation

Jiang, W.,Birtley, J.R.,Hung, S.C.,Wang, W.,Chiou, S.H.,Macaubas, C.,Kornum, B.,Tian, L.,Huang, H.,Adler, L.,Weaver, G.,Lu, L.,Ilstad-Minnihan, A.,Somasundaram, S.,Ayyangar, S.,Davis, M.M.,Stern, L.J.,Mellins, E.D.
In vivo clonal expansion and phenotypes of hypocretin-specific CD4+T cells in narcolepsy patients and controls.
Nat Commun, 10:5247-5247, 2019

PubMed Abstract: Individuals with narcolepsy suffer from abnormal sleep patterns due to loss of neurons that uniquely supply hypocretin (HCRT). Previous studies found associations of narcolepsy with the human leukocyte antigen (HLA)-DQ6 allele and T-cell receptor α (TRA) J24 gene segment and also suggested that in vitro-stimulated T cells can target HCRT. Here, we present evidence of in vivo expansion of DQ6-HCRT tetramer/TRAJ24/CD4 T cells in DQ6 individuals with and without narcolepsy. We identify related TRAJ24 TCRαβ clonotypes encoded by identical α/β gene regions from two patients and two controls. TRAJ24-G allele clonotypes only expand in the two patients, whereas a TRAJ24-C allele clonotype expands in a control. A representative tetramer/G-allele TCR shows signaling reactivity to the epitope HCRT. Clonally expanded G-allele T cells exhibit an unconventional effector phenotype. Our analysis of in vivo expansion of HCRT-reactive TRAJ24 cells opens an avenue for further investigation of the autoimmune contribution to narcolepsy development.

PubMed: 31748512
DOI: 10.1038/s41467-019-13234-x

Experimental method

X-RAY DIFFRACTION (2 Å)