Reconciling the structural attributes of avian antibodies

Paul Conroy, Ruby Hong Ping Law, Sarah Gilgunn, Stephen Hearty, Tom T Caradoc-Davies, Gordon Lloyd, Richard O'Kennedy, James Whisstock

Research output: Contribution to journalArticleResearchpeer-review

19 Citations (Scopus)

Abstract

Antibodies are high value therapeutic, diagnostic, biotechnological and research tools. Combinatorial approaches to antibody discovery have facilitated access to unique antibodies by surpassing the diversity limitations of the natural repertoire, exploitation of immune repertoires from multiple species and tailoring selections to isolate antibodies with desirable biophysical attributes. The V-gene repertoire of the chicken does not utilise highly diverse sequence and structures, which is in stark contrast to the mechanism employed by humans, mice and primates. Recent exploitation of the avian immune system has generated high-quality, high-affinity antibodies to a wide range of antigens for a number of therapeutic, diagnostic and biotechnological applications. Furthermore, extensive examination of the amino acid characteristics of the chicken repertoire has provided a significant insight into mechanisms employed by the avian immune system. A paucity of avian antibody crystal structures has limited our understanding of the structural consequences of these uniquely chicken features. This paper presents the crystal structure of two chicken scFv antibodies generated from large libraries, by phage display, against important human antigen targets, which capture two unique CDRL1 canonical classes in the presence and absence of a non-canonical disulphide constrained CDRH3. These structures cast light on the unique structural features of chicken antibodies and contribute further to our collective understanding of the unique mechanisms of diversity and biochemical attributes that render the chicken repertoire of particular value for antibody generation.
Original languageEnglish
Pages (from-to)15384 - 15392
Number of pages9
JournalThe Journal of Biological Chemistry
Volume289
Issue number22
DOIs
Publication statusPublished - 2014

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