B-cell and T-cell epitopes in anti-factor VIII immune responses

Kathleen P. Pratt, Arthur R. Thompson

Research output: Contribution to journalReview articlepeer-review

29 Scopus citations

Abstract

Adequate hemostasis is achieved for many hemophilia A patients by infusion of plasma-derived or recombinant factor VIII (FVIII), but unfortunately, a significant subset of patients develop an immune response in which anti-FVIII antibodies, referred to clinically as "inhibitors," interfere with its procoagulant activity. Inhibitors are the subset of anti-FVIII antibodies that bind to surfaces on FVIII (B-cell epitopes) that are important for its proper functioning in coagulation. Less antigenic FVIII molecules may be designed by identifying and then modifying the amino acid sequences of inhibitor B-cell epitopes. Conversely, characterization of these epitopes can yield important information regarding functionally important surfaces on FVIII. The production of inhibitor antibodies is driven by T cells. T cells recognize FVIII as foreign when FVIII-derived peptides bind to major histocompatibility complex (MHC) class II molecules on the surface of antigen-presenting cells. The class II-peptide complexes must then be recognized by T-cell receptors (TCRs). T-cell stimulation requires sustained association of antigen-presenting cells and T cells through formation of a class II-peptide-TCR complex, and peptide sequences that mediate this association are termed "T-cell epitopes." MHC class II tetramers that bind FVIII-derived peptides and recognize antigen-specific TCRs are proving useful in the characterization of human leukocyte antigen-restricted T-cell responses to FVIII.

Original languageEnglish
Pages (from-to)80-95
Number of pages16
JournalClinical Reviews in Allergy and Immunology
Volume37
Issue number2
DOIs
StatePublished - Oct 2009
Externally publishedYes

Keywords

  • B-cell epitopes
  • Hemophilia A
  • Inhibitory antibody
  • T-cell immune responses

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