Influence of Lys-residue deletion on the immunomodulatory activity of peptides related to immunosuppressive region of lactoferrin.

The effects of Lys residue deletion from peptides, related to immunosuppressive regions of lactoferrin (LF), were studied in the humoral and cellular immune responses to sheep erythrocytes (SRBC) in mice. We found that the deletion of Lys residue, vicinal to Pro, influences mostly the immunomodulatory activity of short fragments (tetra-, and pentapeptides) of immunosuppressive 231-245 mini-domain of LF. The activity of longer peptides, related to this mini-domain, is influenced to much lower extent by Lys removal. In particular, the tetrapeptide derived from Arg-Lys-Pro-Val-Asp sequence by deletion of Lys, exhibits strongly reduced immunosuppressive activity. On the contrary, the similar change within Arg-Lys-Pro-Val-Thr sequence, derived of 575-589 loop of LF, produces a tetrapeptide Arg-Pro-Val-Thr, that is active as immunosuppressor both in humoral and cellular immune response. A quite strong immunosuppressive activity of tripeptide Lys-Arg-Pro is also worth consideration, especially when compared with the loss of activity observed for Thr-Arg-Pro tripeptide. The data presented herein indicate that exclusion of Lys residue from the LF-derived immunomodulatory peptides differentially alters their effects on the immune response to SRBC in mice.