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Blood, 1 March 2005, Vol. 105, No. 5, pp. 2175-2179.
Prepublished online as a Blood First Edition Paper on September 21, 2004; DOI 10.1182/blood-2004-04-1554.


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Submitted April 27, 2004
Accepted September 16, 2004

Immune responses and tolerance to the RhD blood group protein in HLA-transgenic mice

Andrew M Hall, Lindsay S Cairns, Daniel M Altmann, Robert N Barker, and Stanislaw J Urbaniak*

Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom; Academic Transfusion Medicine Unit, Department of Medicine and Therapeutics, University of Aberdeen, Aberdeen, United Kingdom
Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom
Human Disease Immunogenetics Group, Department of Infectious Diseases, Imperial College, London, United Kingdom

* Corresponding author; email: s.j.urbaniak{at}abdn.ac.uk.

RhD is a major blood group and the most important target antigen in hemolytic disease of the newborn (HDN). The aims 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. Expression of an HLA-DR transgene was found to confer on mice the ability to respond to immunization with purified RhD protein. Synthetic peptides containing dominant helper T-cell epitopes, previously identified from studies of human alloimmunized donors, were administered to the nasal mucosa of transgenic mice prior to immunization with purified RhD protein. Treatment with each of the four dominant peptides, RhD52-66, RhD97-111, RhD117-131, or 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.


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