In patients with inflammatory demyelinating neuropathy, which is possibly mediated by autoreactive, myelin-specific T lymphocytes, most studies focusing on immune responses to the major neuritogenic myelin protein P2 have been performed with bovine P2. However, the primary structure of bovine P2 differs from the human protein by nine amino acid residues that may profoundly influence the antigen recognition by T lymphocytes. We purified bovine and human P2 from peripheral nervous tissue and established a total of 19 T cell lines (TCL) reactive with bovine P2 from blood of two patients with acute Guillain-Barré syndrome (n = 5 TCL) and from six healthy individuals. Only four of these TCL, all raised from the blood of the GBS patients, transiently cross-recognized human P2 protein. Our results suggest that the use of human autoantigen may be crucial for the characterization of T cellular immune responses against P2 protein both in patients with inflammatory demyelinating neuropathy and in healthy controls.