Guillain–Barré syndrome (GBS) is a rare, potentially life-threatening autoimmune disorder of the peripheral nervous system, often triggered by infections. It is characterized by progressive muscle weakness, loss of reflexes, and, in severe cases, respiratory failure. GBS has several subtypes, including acute inflammatory demyelinating polyneuropathy (AIDP), the most common form, and acute motor axonal neuropathy (AMAN). The study identifies autoreactive CD4+ and CD8+ T cells that target myelin antigens in peripheral nerves, contributing to the disease's pathophysiology. These T cells exhibit a cytotoxic T helper 1 (T(H)1)-like phenotype and recognize immunodominant epitopes of peripheral myelin proteins, such as P0, P2, and PMP22. The autoreactive TCRβ repertoire is polyclonal, with short CDR3β lengths and preferential HLA-DR restriction. These T cells are expanded in the blood of patients at different disease stages and are shared among patients but not in healthy individuals. The study also identifies myelin-reactive T cells in nerve biopsies, indicating their direct involvement in disease progression. The findings suggest that autoreactive T cell immunity plays a role in a subset of GBS cases, offering new insights into inflammatory peripheral neuropathies and potential therapeutic targets. The study highlights the importance of autoreactive T cells in GBS pathogenesis and underscores the need for further research into the immune mechanisms underlying the disease.Guillain–Barré syndrome (GBS) is a rare, potentially life-threatening autoimmune disorder of the peripheral nervous system, often triggered by infections. It is characterized by progressive muscle weakness, loss of reflexes, and, in severe cases, respiratory failure. GBS has several subtypes, including acute inflammatory demyelinating polyneuropathy (AIDP), the most common form, and acute motor axonal neuropathy (AMAN). The study identifies autoreactive CD4+ and CD8+ T cells that target myelin antigens in peripheral nerves, contributing to the disease's pathophysiology. These T cells exhibit a cytotoxic T helper 1 (T(H)1)-like phenotype and recognize immunodominant epitopes of peripheral myelin proteins, such as P0, P2, and PMP22. The autoreactive TCRβ repertoire is polyclonal, with short CDR3β lengths and preferential HLA-DR restriction. These T cells are expanded in the blood of patients at different disease stages and are shared among patients but not in healthy individuals. The study also identifies myelin-reactive T cells in nerve biopsies, indicating their direct involvement in disease progression. The findings suggest that autoreactive T cell immunity plays a role in a subset of GBS cases, offering new insights into inflammatory peripheral neuropathies and potential therapeutic targets. The study highlights the importance of autoreactive T cells in GBS pathogenesis and underscores the need for further research into the immune mechanisms underlying the disease.