T lymphocyte recognition sites on peripheral nerve myelin P0 protein

Synthetic peptides corresponding to the extracellular and cytoplasmic domain of bovine (b) or rat (r) peripheral myelin P0 protein were used to establish a total of 50 short-term T cell lines (TCL) from blood of eight healthy subjects. Despite expressing different HLA-DR and HLA-DQ specificities, one or more TCL (range 1-16) specific for peptide bovine P0 19-38 could be isolated from the blood of each donor. Therefore, this peptide covers an immunodominant T cell recognition site in humans. However, when testing seven bP0-19-38-specific TCL derived from blood of two healthy subjects for recognition of the corresponding human P0 sequence, no TCL showed any proliferative response. Bovine P0-19-38 differs in only two amino acid residues from the human peptide. This observation stresses the necessity for using homologous antigens when screening for T cell-mediated autoreactivity to myelin antigens in humans. Unexpectedly, we failed to establish a single P0 peptide-specific TCL from blood of four patients with acute Guillain-Barré syndrome (GBS), in which P0 is considered a putative target autoantigen. As already suggested by others, this could indicate that T cell responses to P0 do not play a pathogenic role in all GBS cases. Alternatively, in these four patients neuritogenic P0-specific T lymphocytes may have been sequestrated to peripheral nerves.