Immune responses and tolerance to the RhD blood group protein in HLA-transgenic mice.
RhD is a major blood group and the most important target antigen in hemolytic disease of the newborn (HDN). The aims of this study were to establish a humanized mouse model of responses to the RhD protein and to test whether these could be prevented by the induction of immune tolerance. HLA-DR15 is a major restricting element for human T-helper (Th) cells specific for RhD protein, and expression of this HLA-DR transgene was found to confer on mice the ability to respond to immunization with purified RhD protein. Synthetic peptides containing dominant Th cell epitopes, previously identified from studies of human alloimmunized donors, were administered to the nasal mucosa of transgenic mice before immunization with purified RhD protein. Treatment with each of the 4 dominant peptides, RhD52-66, RhD97-111, RhD117-131, and RhD177-191, inhibited T-cell priming and prevented antibody responses to the RhD protein. The ability to induce such active tolerance offers the prospect of peptide immunotherapy as a replacement for passive immune globulin in the prophylaxis of HDN.
Hall
Andrew M
AM
Institute of Medical Sciences and Academic Transfusion Medicine Unit, Department of Medicine and Therapeutics, Regional Transfusion Center, Foresterhill Road, Aberdeen AB25 2ZW, United Kingdom.
Cairns
Lindsay S
LS
Altmann
Daniel M
DM
Barker
Robert N
RN
Urbaniak
Stanislaw J
SJ
D000818:Animals; D000917:Antibody Formation; D000939:Epitopes / Q000008:administration & dosage; D006684:HLA-DR Antigens / Q000235:genetics*; D059810:HLA-DR Serological Subtypes; D006801:Humans; D007108:Immune Tolerance; D007114:Immunization / Q000379:methods*; D051379:Mice; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000008:administration & dosage; D012204:Rh-Hr Blood-Group System / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use; D006377:T-Lymphocytes, Helper-Inducer; D019076:Transgenes
D000939:Epitopes; D006684:HLA-DR Antigens; D059810:HLA-DR Serological Subtypes; C106559:HLA-DR15 antigen; D010446:Peptide Fragments; D012204:Rh-Hr Blood-Group System; C026410:Rho(D) antigen