Synthetic peptides from the N-terminal regions of CD200 and CD200R1 modulate immunosuppressive and anti-inflammatory effects of CD200-CD200R1 interaction.
A series of 15-mer peptides were synthesized defining continuous sequences of the extracellular region of the murine and human CD200 molecule. In addition, peptides mapping to the presumptive CDR1, CDR2 and CDR3 of the human and mouse CD200R1 molecules were synthesized. The ability of these various molecules to block the interaction of CD200 with CD200R1 was studied in a competitive ELISA using plate-bound CD200R1Fc and biotinylated CD200Fc, and by FACS using FITC-conjugated CD200Fc binding to 24-h LPS-activated adherent cells. Results from these data were compared with the functional ability of the same peptides to suppress the inhibition of generation of allo-specific CTL in vitro following inclusion of CD200Fc in mixed leukocyte culture reactions. Peptides defining discrete regions in the N terminal regions of CD200 and CD200R1 were functionally active in these different assays. Moreover, infused in vivo, the same mouse-specific peptides suppressed protection from graft rejection afforded by injection of soluble immunosuppressive CD200Fc. Used alone in vitro, these peptides enhanced alloimmunity.
Chen
Dang-Xiao
DX
Transplant Research Division, Toronto Hospital, University Health Network, 200 Elizabeth Street, NU-G001, Toronto, Ontario M5G2C4, Canada.
He
Hao
H
Gorczynski
R M
RM
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD; D000954:Antigens, Surface / Q000737:chemistry* / Q000378:metabolism; D005260:Female; D005803:Genes, Immunoglobulin; D006801:Humans; D007108:Immune Tolerance; D018836:Inflammation Mediators / Q000737:chemistry / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008969:Molecular Sequence Data; D064446:Orexin Receptors; D010455:Peptides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011487:Protein Conformation; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism
D015703:Antigens, CD; D000954:Antigens, Surface; C477337:CD200R1 protein, human; C501103:Cd200r1 protein, mouse; D018836:Inflammation Mediators; D064446:Orexin Receptors; D010455:Peptides; D011956:Receptors, Cell Surface; C042739:antigens, CD200