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...

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Bibliographic Details
Published in:Blood 2005-03, Vol.105 (5), p.2175-2179
Main Authors: Hall, Andrew M., Cairns, Lindsay S., Altmann, Daniel M., Barker, Robert N., Urbaniak, Stanislaw J.
Format: Article
Language:English
Subjects:
Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
Animals
Antibody Formation
Biological and medical sciences
Emergency and intensive care: neonates and children. Prematurity. Sudden death
Epitopes - administration & dosage
HLA-DR Antigens - genetics
HLA-DR Serological Subtypes
Humans
Immune Tolerance
Immunization - methods
Intensive care medicine
Medical sciences
Mice
Mice, Transgenic
Peptide Fragments - administration & dosage
Rh-Hr Blood-Group System - administration & dosage
Rh-Hr Blood-Group System - immunology
Rh-Hr Blood-Group System - therapeutic use
T-Lymphocytes, Helper-Inducer
Transgenes
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Summary: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.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2004-04-1554