Identification of T-cell epitopes in clotting factor IX and lack of tolerance in inbred mice

R. Greenwood, B. Wang, K. Midkiff, G. C. White, H. F. Lin, J. A. Frelinger

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

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{thorn} T cells that proliferate in response to human factor IX. Surprisingly, wild-type mice have similar factor IX-recognizing CD4{thorn} T cells. We defined a dominant CD4{thorn} 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.

Original languageEnglish (US)
Pages (from-to)95-102
Number of pages8
JournalJournal of Thrombosis and Haemostasis
Volume1
Issue number1
DOIs
StatePublished - Jan 1 2003
Externally publishedYes

Keywords

  • Factor IX
  • T-cell epitope

ASJC Scopus subject areas

  • Hematology

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