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The production of monoclonal antibodies using hybridoma technology (Kohler and Milstein, 1975) represents a landmark for the use of antibodies as reagents for medicine and biology. It is now possible to use recombinant DNA methods to isolate and genetically manipulate antibody genes, and the resulting immunoglobulins or immunoglobulin fragments can be efficiently expressed in mammalian or bacterial hosts (for a review, see Morrison et al., 1988).The immunoglobulin molecule consists of a string of domains, each domain consisting of about 100 amino acid residues. The constant domains carry the effector functions, such as complement mediated lysis and ADCC. The antigen binding site is fashioned by both heavy (VH) and light (VL; Vκ or Vλ) chain variable domains, as demonstrated by the solved crystallographic structures of antibody in association with antigen (Amit et al., 1986; Sheriff et al., 1987; Colman et al.,1987) or hapten (Satow et al, 1986). Variable domains have been pasted onto constant domains (Morrison et ah, 1984; Boulianne et al., 1984; Neuberger et al.,1985) and hypervariable loops (CDRs) onto the underlying (β-sheet framework of variable domains (Jones et al.,1986; Verhoeyen et al.,1988; Riechmann et al.,1988a). Grafting CDRs has been used to humanise rodent antibodies and one such antibody used in the successful treatment of 2 patients with non- Hodgkins lymphoma (Hale et al.,1988; Riechmann et al.,1988a). |
