Cyclization of PLP_139-151 peptide reduces its encephalitogenic potential in experimental autoimmune encephalomyelitis

The present experimental study indicates a reduced encephalitogenic effect of cPLP peptide compared to its linear analog.

Our clinical and histopathological data of acute phase (highest disease activity) converge to the fact that cPLP is less potent in causing tissue damage and a consequent of clinical disease.

Of special interest is that mice from both groups with similar inflammatory burden in their spinal cords displayed different clinical severity scores depending on whether they were immunized with the linear of the cyclic peptide (very low scores in the cPLP animals and severe score in the linPLP ones). This is in agreement to the in vitro restimulation data of LNCs, which confirmed the lower stimulatory effects of cPLP compared to the linPLP peptide, and to the reduced in vivo anti-IgG PLP antibody production in cPLP-immunized animals compared to linPLP.

These data collectively indicate that the cyclization of a linear encephalitogenic peptide reduces the activation of lymphocytes and their specificity to their antigenic targets in the CNS tissue.