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Single domain antibodies from llama effectively and specifically block T cell ecto‐ADP‐ribosyltransferase ART2.2 in vivo
Author(s) -
Koch-Nolte Friedrich,
Reyelt Jan,
Schößow Britta,
Schwarz Nicole,
Scheuplein Felix,
Rothenburg Stefan,
Haag Friedrich,
Alzogaray Vanina,
Cauerhff Ana,
Goldbaum Fernando A.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.07-8661com
Subject(s) - in vivo , antibody , enzyme , immune system , chemistry , t cell , microbiology and biotechnology , cytolysis , biology , in vitro , cytotoxic t cell , biochemistry , immunology
The purpose of our study was to develop a tool for blocking the function of a specific leukocyte ecto‐enzyme in vivo. ART2.2 is a toxin‐related ecto‐enzyme that transfers the ADP‐ribose moiety from NAD onto other cell surface proteins. ART2.2 induces T cell death by activating the cytolytic P2×7 purinoceptor via ADP‐ribosylation. Here, we report the generation of ART2.2‐blocking single domain antibodies from an immunized llama. The variable domain of heavy‐chain antibodies (VHH domain) represents the smallest known antigen‐binding unit generated by adaptive immune responses. Their long CDR3 endows VHH domains with the extraordinary capacity to extend into and block molecular clefts. Following intravenous injection, the ART2.2‐specific VHH domains effectively shut off the enzymatic and cytotoxic activities of ART2.2 in lymphatic organs. This blockade was highly specific (blocking ART2.2 but not the related enzymes ART1 or ART2.1), rapid (within 15 min after injection), and reversible (24 h after injection). Our findings constitute a proof of principle that opens up a new avenue for targeting leukocyte ecto‐enzymes in vivo and that can serve as a model also for developing new antidotes against ADP‐ribosylating toxins.—Koch‐Nolte, F., Reyelt, J., Schöβow, B., Schwarz, N., Scheuplein, F., Rothenburg, S., Haag, F., Alzogaray, V., Cauerhff, A., and Goldbaum, F. A. Single domain antibodies from llama effectively and specifically block T cell ecto‐ADP‐ribosyltransferase ART2.2 in vivo. FASEB J. 21, 3490–3498 (2007)

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