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6DIG

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

Summary for 6DIG
Entry DOI10.2210/pdb6dig/pdb
DescriptorMHC 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 Keywordsmhc class ii hla, immune system
Biological sourceHomo sapiens (Human)
More
Total number of polymer chains3
Total formula weight49810.37
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: 2023-10-11)
Primary citationJiang, 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
Cited by
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
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (2 Å)
Structure validation

226707

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