Monoclonal and recombinant antibodies with T cell receptor-like reactivity.

Ziegler, Andreas;Coulie, Pierre;Uchańska-Ziegler, Barbara
(2007) Recent Results in Cancer Research — Vol. 176, p. 229-241 (2007)

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Authors
  • Ziegler, Andreas
    Author
  • Author
  • Uchańska-Ziegler, Barbara
    Author
Abstract
We will explain why major histocompatibility complex (MHC) molecules presenting peptides derived from tumour-associated antigens can be recognized not only by T cell receptors (TCR), but also by soluble proteins endowed with TCR-like reactivity. To understand how an antibody can display high affinity and specificity for a particular MHC:peptide complex, we have employed X-ray crystallography to determine the structure of a recombinant antibody, Hyb3, bound to human HLA-A1 molecules presenting the peptide EADPTGHSY that is derived from the tumour-associated antigen MAGE-Al. The results indicate that although Hyb3 recgonizes its target in a TCR-like diagonal binding mode, important differences between the two types of proteins exist that are probably due to the fact that TCR are part of a molecular assembly on the surface of effector cells, while antibodies such as Hyb3 have to carry out their function as individual molecules.
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Ziegler, A., Coulie, P., & Uchańska-Ziegler, B. (2007). Monoclonal and recombinant antibodies with T cell receptor-like reactivity. Recent Results in Cancer Research, 176, 229-241. https://doi.org/10.1007/978-3-540-46091-6_20 (Original work published 2007)