Dissecting the CD8 T cell reactivity in Narcolepsy type 1

Narcolepsy type 1 (NT1) is a sleep disorder caused by the loss of signalling through the sleep-regulating neuropeptide hypocretin. Epidemiological, experimental and genetic data – such as the very strong correlation to the HLA class II allele, HLA-DQB1*06:02 – suggests that NT1 is an autoimmune disease targeting the hypocretin producing neurons. In a previous study published in Nature Communications, we identified CD8 T cell recognition of peptides with relevance for NT1, in the blood of 20 NT1 patients and 52 healthy controls. By using barcoded MHC multimers, we screened for recognition of 1183 predicted peptides from 7 different proteins expressed within hypocretin neurons. We found that the frequency of autoreactive CD8 T cells was significantly lower in healthy donors expressing the risk allele HLA-DQB1*06:02 than in both NT1 patients and healthy donors negative for HLA-DQB1*06:02. This suggests that a certain level of CD8 T cell reactivity combined with HLA-DQB1*06:02 expression plays a role in NT1 development. In the present study we are looking for CD8 T cell reactivity towards the same 1183 NT1 relevant peptides in cerebrospinal fluid (CSF) and blood samples from 7 patients with recent onset NT1 and 7 healthy donors. Furthermore, the MHC multimer analysis is combined with an extensive phenotyping panel to inform us on the type of CD8 T cells present in the donor samples. The results will further enhance our understanding of the pathogenesis of NT1.