Structural highlights
Publication Abstract from PubMedIndividuals 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 alpha (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(+) TCRalphabeta clonotypes encoded by identical alpha/beta 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 HCRT87-97. 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. In vivo clonal expansion and phenotypes of hypocretin-specific CD4(+) T cells in narcolepsy patients and controls.,Jiang W, Birtley JR, Hung SC, Wang W, Chiou SH, Macaubas C, Kornum B, Tian L, Huang H, Adler L, Weaver G, Lu L, Ilstad-Minnihan A, Somasundaram S, Ayyangar S, Davis MM, Stern LJ, Mellins ED Nat Commun. 2019 Nov 20;10(1):5247. doi: 10.1038/s41467-019-13234-x. PMID:31748512[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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