Prevention of graft-versus-host disease by peptides binding to class II major histocompatibility complex molecules.
Graft-versus-host disease across minor histocompatibility barriers was induced in two different models by transplanting allogeneic bone marrow and spleen cells into irradiated H-2-compatible recipient mice. In this report, we show that administration of peptides with high binding affinity for the respective class II major histocompatibility complex molecules after transplantation is capable of preventing the development of graft-versus-host disease in two different murine models. The peptides used were myelin basic protein residues 1 through 11 with alanine at position 4 (Ac 1-11[4A]) for I-Au (A alpha uA beta u), and the antigenic core sequence 323 through 339 of ovalbumin with lysine and methionine extension (KM core) for I-As (A alpha sA beta s). In both systems, the mechanism of prevention was found to be major histocompatibility complex-associated, because nonbinding control peptides did not have any effect. Engraftment of allogeneic bone marrow cells was shown by polymerase chain reaction analysis of DNA polymorphisms in a microsatellite region within the murine interleukin-5 gene.
Schlegel
P G
PG
Bone Marrow Transplantation Program, Stanford University School of Medicine, CA.
Aharoni
R
R
Smilek
D E
DE
Fernandez
L P
LP
McDevitt
H O
HO
Tran
N
N
Vaysburd
M
M
Chao
N J
NJ
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D016026:Bone Marrow Transplantation; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control*; D006183:H-2 Antigens / Q000032:analysis / Q000276:immunology; D006648:Histocompatibility; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D015848:Interleukin-5 / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000737:chemistry / Q000627:therapeutic use; D010047:Ovalbumin / Q000737:chemistry / Q000627:therapeutic use; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use*; D016133:Polymerase Chain Reaction; D012091:Repetitive Sequences, Nucleic Acid; D013154:Spleen / Q000637:transplantation; D013601:T-Lymphocytes / Q000276:immunology
D006183:H-2 Antigens; D000949:Histocompatibility Antigens Class II; D015848:Interleukin-5; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D010047:Ovalbumin