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Mapping of the epitope of monoclonal antibody 2B4 to the proline‐rich region of human Huntingtin, a region critical for aggregation and toxicity
Author(s) -
Dehay Benjamin,
Weber Chantal,
Trottier Yvon,
Bertolotti Anne
Publication year - 2007
Publication title -
biotechnology journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.144
H-Index - 84
eISSN - 1860-7314
pISSN - 1860-6768
DOI - 10.1002/biot.200600249
Subject(s) - huntingtin , epitope , huntingtin protein , monoclonal antibody , antibody , amino acid , biology , mutant , epitope mapping , microbiology and biotechnology , chemistry , biochemistry , genetics , gene
Huntington's disease is a neurodegenerative disease caused by a polyglutamine (polyQ) expansion in Huntingtin, which provokes aggregation of a proteolytic amino‐terminal fragment of the affected protein encompassing the polyQ expansion. Accumulation of mutant Huntingtin somehow triggers cellular dysfunction and leads to a progressive degeneration of striatal neurons. Despite considerable efforts, the function of Huntingtin as well as the precise molecular mechanisms by which the expanded polyQ elicits cellular dysfunction remain unclear. In addition, no treatment is available to prevent, cure, or even slow down the progression of this devastating disorder. Antibodies are valuable tools to understand protein function and disease mechanisms. Here, we have identified the epitope recognized by the mAb 2B4, a broadly used antibody generated against the amino‐terminal region of Huntingtin, which detects both aggregated and soluble Huntingtin. The 2B4 antibody specifically recognizes amino acids 50–64 of human Huntingtin but not the murine homologous region. Furthermore, the 2B4 epitope resides within the proline‐rich region of Huntingtin, which is critical for polyQ aggregation and toxicity. These properties suggest that the 2B4 antibody might be useful in antibody‐based therapeutic strategies.