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Review
. 2019 Dec;35(12):1098-1105.
doi: 10.1051/medsci/2019218. Epub 2020 Jan 6.

[The hinge region of therapeutic antibodies: major importance of a short sequence]

[Article in French]
Quentin Deveuve  1 , Valérie Gouilleux-Gruart  2 , Gilles Thibault  2 , Laurie Lajoie  1
Affiliations
Free article
Review

[The hinge region of therapeutic antibodies: major importance of a short sequence]

[Article in French]
Quentin Deveuve et al. Med Sci (Paris). 2019 Dec.
Free article

Abstract
in English, French

The hinge region is a short sequence of the heavy chains (H) of antibodies linking the Fab (Fragment antigen binding) region to the Fc (Fragment crystallisable) region. The functional properties of the four IgG subclasses partly result from the sequence differences of their hinge regions as some amino acids of the lower hinge region are located within or in the close vicinity of the C1q and FcγR binding sites on the IgG H chains. In addition, the hinge is susceptible to proteolytic cleavage by many proteases present in tumor and/or inflammatory microenvironment capable of affecting functional responses. Thus, an optimal format of the hinge region remains a major challenge for the development of new therapeutic antibodies.

Title: La région charnière des anticorps thérapeutiques - L’importance capitale d’une courte séquence.

Abstract: La région charnière est une courte séquence des chaînes lourdes (H) d’anticorps liant le Fab (fragment antigen binding) au Fc (fragment crystallisable). Les propriétés fonctionnelles des quatre sous-classes d’immunoglobulines d’isotype G (IgG) résultent en partie des différences de séquence de leurs régions charnières. En effet, certains acides aminés de la partie C-terminale de ces régions charnières (« partie basse ») sont situés au sein ou à proximité des sites de liaison de la molécule C1q de la voie classique du complément et des récepteurs pour la région Fc des IgG (RFcγ) sur les chaînes H d’IgG. Les régions charnières sont également sensibles au clivage protéolytique par de nombreuses protéases du microenvironnement tumoral et/ou inflammatoire pouvant altérer les réponses fonctionnelles. Le format optimal de la charnière reste donc un défi majeur pour le développement de nouveaux anticorps thérapeutiques.

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References

    1. Burton DR , Immunoglobulin G: functional sites. Mol Immunol. 1985;22:161–206.
    1. Ugurlar D, Howes SC, de Kreuk BJ, et al., Structures of C1-IgG1 provide insights into how danger pattern recognition activates complement. Science. 2018;359:794–7.
    1. Strasser J, De Jong RN, Beurskens FJ, et al., Unraveling the macromolecular pathways of IgG oligomerization and complement activation on antigenic surfaces. Nano Lett. 2019;19:4787–96.
    1. Bindon CI , Human monoclonal IgG isotypes differ in complement activating function at the level of C4 as well as C1q. J Exp Med. 1988;168:127–42.
    1. Morgan A, Jones ND, Nesbitt AM, et al., The N-terminal end of the CH2 domain of chimeric human IgG1 anti-HLA-DR is necessary for C1q, Fc gamma RI and Fc gamma RIII binding. Immunology. 1995;86:319–24.

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