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.

我们报告了环状PLP _139-151（cPLP）的新型合成及其在SJL / J小鼠中的应用，以研究其致脑病作用。我们的结果表明，当cPLP类似物被诱导诱发实验性自身免疫性脑脊髓炎时，其致脑病作用最小（与线性对应物相比，疾病负担低，炎症，脱髓鞘和轴索病理性疾病的发生率低）。增殖测定证实与linPLP相比，cPLP的刺激潜力低（增殖低2.5倍），并诱导了较低的抗体应答。分子建模显示，与linPLP相比，cPLP的TCR识别特性完全不同，其中H ¹⁴⁷代替W ¹⁴⁴，F ¹⁵¹ -K ¹⁵⁰代替HTCR接触为¹⁴⁷，这可能解释了每种肽反应的差异。