Myelin proteolipid protein: minimum sequence requirements for active induction of autoimmune encephalomyelitis in SWR/J and SJL/J mice

Abstract

Proteolipid protein (PLP) is the major protein constituent of mammalian central nervous system myelin. We have previously identified two different PLP encephalitogenic T cell epitopes in two mouse strains. Murine PLP peptides 103–116 YKTTICGKGLSATV and 139–151 HCLGKWLGHPDKF are encephalitogenic determinants in SWR/J (H-2 q) and SJL/J (H-2 s) mice, respectively. The purpose of the present study was to determine the minimum sequence requirements for each of these PLP encephalitogens. In SWR/J mice, at least two distinct overlapping peptides can induce experimental autoimmune encephalomyelitis (EAE). The eleven residue sequences PLP 105–115 TTICGKGLSAT and PLP 106–116 TICGKGLSATV are encephalitogenic in SWR/J mice, but PLP 106–115 TICGKGLSAT, the decapeptide indigenous to both sequences, is non-encephalitogenic. In contrast, the shortes PLP sequence capable of inducing EAE in SJL/J mice is the nonapeptide 141–149 LGKWLGHPD. These data indicate that encephalitogenic determinants of PLP are short contiguous peptide sequences similar in length and diversity to those of MBP.