PMID- 35914171
OWN - NLM
STAT- MEDLINE
DCOM- 20220803
LR  - 20220927
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 119
IP  - 32
DP  - 2022 Aug 9
TI  - Characterization of T cell receptors reactive to HCRT(NH2), pHA(273-287), and 
      NP(17-31) in control and narcolepsy patients.
PG  - e2205797119
LID - 10.1073/pnas.2205797119 [doi]
LID - e2205797119
AB  - Narcolepsy type 1 (NT1), a disorder caused by hypocretin/orexin (HCRT) cell loss, 
      is associated with human leukocyte antigen (HLA)-DQ0602 (98%) and T cell receptor 
      (TCR) polymorphisms. Increased CD4(+) T cell reactivity to HCRT, especially 
      DQ0602-presented amidated C-terminal HCRT (HCRT(NH2)), has been reported, and 
      homology with pHA(273-287) flu antigens from pandemic 2009 H1N1, an established 
      trigger of the disease, suggests molecular mimicry. In this work, we extended 
      DQ0602 tetramer and dextramer data to 77 cases and 44 controls, replicating our 
      prior finding and testing 709 TCRs in Jurkat 76 T cells for functional 
      activation. We found that fewer TCRs isolated with HCRT(NH2) ( approximately 11%) versus 
      pHA(273-287) or NP(17-31) antigens ( approximately 50%) were activated by their ligand. 
      Single-cell characterization did not reveal phenotype differences in influenza 
      versus HCRT(NH2)-reactive T cells, and analysis of TCR CDR3alphabeta sequences showed 
      TCR clustering by responses to antigens but no cross-peptide class reactivity. 
      Our results do not support the existence of molecular mimicry between HCRT and 
      pHA(273-287) or NP(17-31).
FAU - Luo, Guo
AU  - Luo G
AD  - Center for Sleep Sciences and Medicine, Stanford University School of Medicine, 
      Palo Alto, CA 94304.
FAU - Zhang, Jing
AU  - Zhang J
AD  - Center for Sleep Sciences and Medicine, Stanford University School of Medicine, 
      Palo Alto, CA 94304.
FAU - Lin, Ling
AU  - Lin L
AUID- ORCID: 0000-0002-3406-0058
AD  - Center for Sleep Sciences and Medicine, Stanford University School of Medicine, 
      Palo Alto, CA 94304.
FAU - Mignot, Emmanuel Jean-Marie
AU  - Mignot EJ
AUID- ORCID: 0000-0002-6928-5310
AD  - Center for Sleep Sciences and Medicine, Stanford University School of Medicine, 
      Palo Alto, CA 94304.
LA  - eng
GR  - AI144798-01A1/HHS | NIH | National Institute of Allergy and Infectious Diseases 
      (NIAID)/
PT  - Journal Article
DEP - 20220801
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (HCRT protein, human)
RN  - 0 (Orexins)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 0 (Viral Proteins)
SB  - IM
MH  - Humans
MH  - *Influenza A Virus, H1N1 Subtype/immunology
MH  - Influenza, Human
MH  - *Narcolepsy/immunology/physiopathology
MH  - *Orexins/metabolism
MH  - *Receptors, Antigen, T-Cell/genetics/immunology
MH  - Viral Proteins/immunology
PMC - PMC9371724
OTO - NOTNLM
OT  - DQ0602
OT  - TCR
OT  - hypocretin
OT  - narcolepsy
OT  - tetramer
COIS- Competing interest statement: E.J.-M.M. and B.K. are co-authors on a current 
      (2022) genome-wide association study.
EDAT- 2022/08/02 06:00
MHDA- 2022/08/04 06:00
PMCR- 2022/08/01
CRDT- 2022/08/01 15:23
PHST- 2022/08/01 15:23 [entrez]
PHST- 2022/08/02 06:00 [pubmed]
PHST- 2022/08/04 06:00 [medline]
PHST- 2022/08/01 00:00 [pmc-release]
AID - 202205797 [pii]
AID - 10.1073/pnas.2205797119 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2022 Aug 9;119(32):e2205797119. doi: 
      10.1073/pnas.2205797119. Epub 2022 Aug 1.