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Identification of T‐cell epitopes in clotting factor IX and lack of tolerance in inbred mice
Author(s) -
Greenwood R.,
Wang B.,
Midkiff K.,
White Ii G. C.,
Lin HF.,
Frelinger J. A.
Publication year - 2003
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1046/j.1538-7836.2003.00001.x
Subject(s) - factor ix , epitope , clotting factor , biology , knockout mouse , immune system , antibody , immunology , microbiology and biotechnology , gene , medicine , genetics
Summary. Immune responses to the factor IX protein pose problems for hemophilia B patients who develop antibodies against factor IX and for potential future treatment with gene therapy. To better define the response to human factor IX, we analyzed T‐cell responses to human factor IX in factor IX knockout mice on BALB/c and C57BL/6 (B6) backgrounds, both strains having CD4+ T cells that proliferate in response to human factor IX. Surprisingly, wild‐type mice have similar factor IX‐recognizing CD4+ T cells. We defined a dominant CD4+ epitope for each strain (CVETGVKITVVAGEH for BALB/c and LLELDEPLVLNSYVTPIC for B6) that was recognized by both factor IX knockout and wild‐type mice. While human factor IX did not cross‐react with the mouse homologs of these epitopes, immunization with peptides from murine factor IX stimulated proliferation in factor IX knockout mice and wild‐type mice, demonstrating a failure to delete murine factor IX‐specific T cells in normal mice.