Cyclization of PLP139-151 peptide reduces its encephalitogenic potential in experimental autoimmune encephalomyelitis

Abstract

We report the novel synthesis of cyclic PLP_139-151 (cPLP) and its application in SJL/J mice to study its encephalitogenic effects. Our results indicate that the cPLP analog is minimally encephalitogenic when administered to induce experimental autoimmune encephalomyelitis (low disease burden, minimal inflammatory, demyelinating and axonopathic pathology compared to its linear counterpart). Proliferation assays confirmed the low stimulatory potential of the cPLP compared to linPLP (2.5-fold lower proliferation) as well as inducing lower antibody responses. Molecular modeling showed a completely different TCR recognition profile of cPLP in regard to linPLP, where H¹⁴⁷ replaces W¹⁴⁴ and F¹⁵¹-K¹⁵⁰ replace H¹⁴⁷ as TCR contacts, which may explain the difference on each peptide's response.

Keywords: Cyclic PLP peptide; Cyclic peptide; Experimental autoimmune encephalomyelitis; Multiple sclerosis; Proteolipid.