Abonnement à la biblothèque: Guest
Portail numérique Bibliothèque numérique eBooks Revues Références et comptes rendus Collections
Critical Reviews™ in Immunology
Facteur d'impact: 1.352 Facteur d'impact sur 5 ans: 3.347 SJR: 0.657 SNIP: 0.55 CiteScore™: 2.19

ISSN Imprimer: 1040-8401
ISSN En ligne: 2162-6472

Volume 39, 2019 Volume 38, 2018 Volume 37, 2017 Volume 36, 2016 Volume 35, 2015 Volume 34, 2014 Volume 33, 2013 Volume 32, 2012 Volume 31, 2011 Volume 30, 2010 Volume 29, 2009 Volume 28, 2008 Volume 27, 2007 Volume 26, 2006 Volume 25, 2005 Volume 24, 2004 Volume 23, 2003 Volume 22, 2002 Volume 21, 2001 Volume 20, 2000 Volume 19, 1999 Volume 18, 1998 Volume 17, 1997 Volume 16, 1996 Volume 15, 1995 Volume 14, 1994

Critical Reviews™ in Immunology

DOI: 10.1615/CritRevImmunol.v19.i3.30
42 pages

Structure, Activity, and Immune (T and B Cell) Recognition of Botulinum Neurotoxins

M. Zouhair Atassi
Baylor College of Medicine Houston, TX 77030
Minako Oshima
Departments of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas


Botulism, which was first reported over a century ago, is caused by botulinum neurotoxins produced by Clostridium botulinum in seven immunological serotypes (A through G). The primary structures of a number of these BoNTs have been determined and are reviewed here, together with their gene structure and synthesis. The biological actions of BoNTs, which result in their ability to block neurotransmitter release have been the subject of intensive study, and in this review we discuss the binding of BoNTs to the cell surface as well as the mechanism of their intercellular action. The ability of BoNTs to block neurotransmitter release has been exploited in therapeutic applications to reduce muscle hyperactivity for the treatment of a variety of clinical conditions associated with involuntary muscle spasm and contractions. The advantages, limitations, and risks of these applications are discussed. Certain compounds provide some limited protection against BoNT. However, more effective protection has been obtained immunologically either by passive immunity (i.e., by administration of anti-BoNT Abs) or by immunization with inactivated toxin. More recently, excellent protec¬tion has been obtained by immunization with the receptor-binding region comprising the C-terminal (residues 860 to 1296) fragment (HC) of the heavy chain of BoNT/A. Here we review the mapping of the epitopes on the Hc region of BoNT/A that are recognized by anti-BoNT/A Abs raised in horse, human, and mouse. The epitopes on the HC that are recognized by anti-HC Abs and by HC-primed T lymphocytes were mapped in two mouse strains [BALB/c (H-2d) and SJL (H-2S)]. The peptides, which contain Ab or T cell epitopes (or both) on the HC, were used as immunogens in BALB/c and SJL mice and we identified those peptides whose Ab and/or T-cell responses cross-react with HC. Identification of these peptides is an important first step in the intricate requirements for the design of a synthetic vaccine.