Guillain–Barré syndrome (GBS) is a rare and potentially life-threatening disorder of the peripheral nervous system, often triggered by preceding infections. The mechanisms underlying its distinct clinical subtypes remain largely unknown. This study combines in vitro T cell screening, single-cell RNA sequencing, and T cell receptor (TCR) sequencing to identify autoreactive memory CD4+ and rare CD8+ T cells targeting myelin antigens in patients with the demyelinating disease variant of GBS. Over 1,000 autoreactive single T cell clones were characterized, revealing a polyclonal TCR repertoire, short CDR3β lengths, preferential HLA-DR restrictions, and recognition of immunodominant epitopes. Autoreactive TCRβ clonotypes were expanded in the blood of patients at different disease stages and shared across different patients with GBS but not in controls. Myelin-reactive T cells were also identified in nerve biopsy from one patient, indicating their direct contribution to disease pathophysiology. These findings provide clear evidence of autoreactive T cell immunity in a subset of GBS patients and open new perspectives for understanding inflammatory peripheral neuropathies.Guillain–Barré syndrome (GBS) is a rare and potentially life-threatening disorder of the peripheral nervous system, often triggered by preceding infections. The mechanisms underlying its distinct clinical subtypes remain largely unknown. This study combines in vitro T cell screening, single-cell RNA sequencing, and T cell receptor (TCR) sequencing to identify autoreactive memory CD4+ and rare CD8+ T cells targeting myelin antigens in patients with the demyelinating disease variant of GBS. Over 1,000 autoreactive single T cell clones were characterized, revealing a polyclonal TCR repertoire, short CDR3β lengths, preferential HLA-DR restrictions, and recognition of immunodominant epitopes. Autoreactive TCRβ clonotypes were expanded in the blood of patients at different disease stages and shared across different patients with GBS but not in controls. Myelin-reactive T cells were also identified in nerve biopsy from one patient, indicating their direct contribution to disease pathophysiology. These findings provide clear evidence of autoreactive T cell immunity in a subset of GBS patients and open new perspectives for understanding inflammatory peripheral neuropathies.