A CD4 Domain 1 CC′ Loop Peptide Analogue Enhances Engraftment in a Murine Model of Bone Marrow Transplantation with Sublethal Conditioning

Host CD4+ T cells that survive sublethal or even lethal preconditioning regimens can participate in the process of hematopoietic stem cell graft rejection, particularly when the transplantations are performed across a major histocompatibility complex (MHC) class II barrier. To enhance donor marrow engraftment, we tested the efficacy of a small synthetic cyclic heptapeptide, 802-2 (CNSNQIC), which was designed to closely mimic the CD4 domain 1 CC′ surface loop, theoretically involved in CD4/MHC class II complex oligomerization and subsequent CD4+ T-cell activation. Previously, this peptide was found to have inhibitory activity in murine models for CD4+ T cell-dependent graft-versus-host disease and skin allograft rejection. Herein, we used the MHC class II--disparate bm12 → B6-CD45.1 sublethal irradiation transplantation model to test the possibility that the 802-2 peptide could enhance the engraftment of donor T cell-depleted bone marrow (ATBM). Sublethally irradiated B6-CD45.1 mice that received bm12 ATBM in combination with the 802-2 peptide demonstrated increased donor marrow cell engraftment as compared with mice that received ATBM alone; this suggests that the 802-2 peptide may be useful as an immunomodulating agent to overcome MHC class II mismatch barriers in hematopoietic stem cell transplantation.