Humanization of an anti-lymphocyte function-associated antigen (LFA)-1 monoclonal antibody and reengineering of the humanized antibody for binding to rhesus LFA-1
| Autor: | W A, Werther, T N, Gonzalez, S J, O'Connor, S, McCabe, B, Chan, T, Hotaling, M, Champe, J A, Fox, P M, Jardieu, P W, Berman, L G, Presta |
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| Rok vydání: | 1996 |
| Předmět: |
Keratinocytes
Models Molecular Pan troglodytes Protein Conformation Molecular Sequence Data Immunoglobulin Variable Region In Vitro Techniques Protein Engineering Mice Species Specificity Antibody Specificity Cell Adhesion Animals Humans Amino Acid Sequence Cloning Molecular DNA Primers Binding Sites Base Sequence Sequence Homology Amino Acid Antibodies Monoclonal Intercellular Adhesion Molecule-1 Macaca mulatta Lymphocyte Function-Associated Antigen-1 Recombinant Proteins Mutagenesis Insertional Lymphocyte Culture Test Mixed |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 157(11) |
| ISSN: | 0022-1767 |
| Popis: | Lymphocyte function-associated antigen 1 (LFA-1; CD11a/CD18) is involved in leukocyte adhesion during cellular interactions essential for immunologic responses and inflammation. mAbs against LFA-1 have been shown to inhibit several T cell-dependent immune functions in vitro and prevent graft failure after bone marrow transplantation in vivo. A murine anti-human CD11a mAb, MHM24, has been humanized and shown to prevent adhesion of human T cells to human keratinocytes and the proliferation of T cells in response to nonautologous leukocytes in the mixed lymphocyte response assay. However, of the nonhuman primate CD11a that we tested, the murine and humanized mAbs cross-reacted only with chimpanzee CD11a. To have a mAb available for preclinical studies in rhesus monkeys, the humanized mAb was reengineered to bind to rhesus CD11a by changing four residues in one of the complementarity-determining regions, CDR-H2, in the variable heavy domain. Cloning and molecular modeling of rhesus CD11a I-domain suggested that the changes from Lys197 and/or Arg189 in human CD11a I-domain to Glu197 and Gln189 in rhesus CD11a I-domain may be the reason that rhesus CD11a does not bind to the murine and humanized mAbs. |
| Databáze: | OpenAIRE |
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