Identification of T-cell epitopes in clotting factor IX and lack of tolerance in inbred mice. J Thromb Haemost 2003 Jan;1(1):95-102
Date
07/23/2003Pubmed ID
12871545DOI
10.1046/j.1538-7836.2003.00001.xScopus ID
2-s2.0-0141818963 (requires institutional sign-in at Scopus site) 16 CitationsAbstract
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.
Author List
Greenwood R, Wang B, Midkiff K, White GC 2nd, Lin HF, Frelinger JAAuthor
Gilbert C. White MD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Amino Acid SequenceAnimals
CD4-Positive T-Lymphocytes
Cross Reactions
Epitopes, T-Lymphocyte
Factor IX
Humans
Immune Tolerance
Immunization
Immunoglobulin G
Lymphocyte Activation
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
Molecular Sequence Data
Peptide Fragments
Recombinant Proteins
Sequence Homology, Amino Acid
