Type 1 narcolepsy (T1N) is caused by a loss of hypocretin (HCRT) neurons. Association with HLA DQB1*06:02/DQA1*01:02 (98% vs 25%) heterodimer (DQ0602), T cell receptor (TCR) and other immune loci suggest autoimmunity but autoantigens are unknown. Onset is seasonal in children and associated with influenza-A. During the 2009-10 season, cases were triggered by pH1N12009 Pandemrix vaccination in Europe. We screened 966 peptides derived from 1) Pandemrix vaccine 2) H1N1, and 3) HCRT and RFX4, autoantigens primarily expressed in HCRT neurons for DQ0602 binding, identifying 109 binders. Screening cognate tetramer-specific CD4+ T cells in 6 DQ0602 T1N (5 post-Pandemrix, one recent onset) and 4 post-Pandemrix controls showed differential reactivity to 3 immunodominant influenza epitopes, one from pH1N12009 (pHA273-287) and two from vaccine backbone strain PR8 (NP17-31 and NP261-275). Among autoantigens, we discovered extensive reactivity to C-amidated but not native version of HCRT54-66 and HCRT86-97, two highly homologous peptides, suggesting reduced CD4+ tolerance for post-translational modifications of HCRT. Replication in 35 cases and 22 controls showed higher frequency of tetramer positive CD4+ cells for pHA273-287, NP17-31 and HCRT54-66-NH2 but not NP261-275 or HCRT86-97-NH2. Single cell TCR sequencing revealed TCRalpha/beta usage biases consistent with in-vitro clonal expansion. TCRalpha/beta CDR3 motifs found in pHA273-287, NP17-31 tetramer positive CD4+ cells were also found in INFgamma secreting CD4+ cells stimulated with Pandemrix, confirming dominance in DQ0602-mediated influenza responses. Usage of NP17-31 specific CD4+ cells was biased toward Vβ4-2, a segment increased by narcolepsy-associated Single Nucleotide Polymorphism (SNP) rs1008599. TCRα/β CDR3 motifs of HCRT54-66-NH2 and HCRT86-97-NH2 tetramers were often shared and more diverse. Particularly notable was extensive sharing of a single CDR3α (associated with various CDR3beta using TRAJ24, a chain modulated by SNPs rs1154155 and rs1483979, two SNPs strongly associated with T1N. This particular CDR3 was not enriched in TCRs isolated with pHA273-287 or other flu epitopes so that mimicry with these sequences is still uncertain. Higher HCRT54-66-NH2 and HCRT86-97-NH2 positive CD4+ T cell numbers in T1N together with J24 usage in the corresponding TCRs, suggest that DQ0602-mediated CD4+ responses to HCRT are causal to T1N. Our results provide the first evidence for autoimmunity and flu involvement in T1N pathophysiology.