T-LYMPHOCYTE RECOGNITION SITES ON PERIPHERAL-NERVE MYELIN P-0 PROTEIN

Synthetic peptides corresponding to the extracellular and cytoplasmic domain of bovine (b) or rat (r) peripheral myelin P-0 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 P-0 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 bP(0)-19-38-specific TCL derived from blood of two healthy subjects for recognition of the corresponding human P-0 sequence, no TCL showed any proliferative response. Bovine P-0-19-38 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 P-0 peptide-specific TCL from blood of four patients with acute Guillain-Barr' syndrome (GBS), in which P-0 is considered a putative target autoantigen. As already suggested by others, this could indicate that T cell responses to P-0 do not play a pathogenic role in all GBS cases. Alternatively, in these four patients neuritogenic P-0-specific T lymphocytes may have been sequestrated to peripheral nerves.