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 of TCRα/β revealed usage biases consistent with in-vitro clonal expansion. TCRα/β CDR3 motifs found in pHA273-287, NP17-31 tetramer positive CD4+ cells were also found in INFγ 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 CDR3β) 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.