Abstract
The production of monoclonal antibodies using hybridoma technology (Köhler 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).
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Keywords
- Complement Mediate Lysis
- Keyhole Limpet Haemocyanin
- Antigen Binding Activity
- Hypervariable Loop
- Chain Variable Domain
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
References
Amit AG, Mariuzza RA, Phillips SEV, Poljak RJ (1986) Science 233:747–754
Better M, Chang CP, Robinson RR, Horwitz AH (1988) Science 240:1041–1043
Boulianne GL, Hozumi N, Shulman MJ (1984) Nature 312:643–646
Chothia C, Lesk AM, Dodson GG, Hodgkin DC (1983) Nature 302:500–505
Colman PM, Laver WG, Varghese JN, Baker AT, Tulloch PA, Air GM, Webster RG (1987) Nature 326:358–362
Edmundson AB, Ely KR, Herron JN Molecular Immunology (1984) 21:561–576
Evan GI, Lewis GK, Ramsay G, Bishop JM (1985) Mol Cell Biol 5:3610–3616.
Fearnley IM, Runswick MJ, Walker, JE EMBO J (1989) 8:665–672
Fleischman JB, Porter RR, Press EM, Biochem J (1963) 88:220–228
Getzoff ED, Geysen HM, Rodda SJ, Alexander H, Tainer JA, Lerner RA Science (1987) 235:1191–1196
Gronenborn B Molec Gen Gen (1976) 148:243–250
Hale G, Dyer MJS, Clark MR, Phillips JM, Marcus R, Riechmann L, Winter G, Waldmann H The Lancet (1988) December 17:1394–1399
Jaton J-C, Klinman NR, Givol D, Sela M Biochemistry (1968) 7:4185–4195
Jones PT, Dear PH, Foote J, Neuberger MS, Winter G Nature (1986) 321:522–525
Kabat EA, Wu TT, Reid-Miller M, Gottesman KS in Sequences of Proteins of Immunological Interest (US Dept of Health and Human Services, US Government Printing Office, 1987) Köhler G, Milstein C Nature (1975) 256:495–497
Laemmli UK Nature (London) (1970) 227:680–685
Levison SA, Kierszenbaum F, Dandliker WB Biochemistry (1970) 9:322–331
Maniatis T, Fritsch EF, Sambrook J (eds.) in “Molecular Cloning; a Laboratory Manual” (Cold Spring Harbour 1982) Matsudaira PJ Biol Chem (1987) 262:10035–10038
Miller JH Experiments in Molecular Genetics, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York (1972)
Morrison SL, Johnson MJ, Herzenberg LA, Oi VT Proc Nad Acad Sci USA (1984) 81:6351–6855
Morrsion SL, Wims, LA, Wallick S, Tan L, Oi VT Ann NY Acad Sci (1988) 507:187–198
Munro S, Pelham H Cell (1986) 46:291–300
Neuberger MS, Williams GT, Mitchell EB, Jouhal SS, Flanagan JG, Rabbitts TH Nature (1985) 314:268–270
Orlandi R, Gussow DH, Jones PT, Winter G Proc Natl Acad Sci USA (1989) 86:3833–3837
Riechmann L, Clark M, Waldmann H, Winter G Nature (1988a) 332:323–327
Riechmann L, Foote J, Winter G J Mol Biol (1988b) 203:825–828
Rossman MG et al., Nature (1985) 317:145–153.
Saiki RK, Scharf S, Faloona F, Mullis KB, Horn GT, Erlich HA, Arnheim N Science (1985) 230:1350–1354
Satow Y, Cohen GH, Padlan EA, Davies DR J Mol Biol (1986) 190:593–604.
Sheriff S, Silverton EW, Padlan EA, Cohen GH, Smith-Gill SJ, Finzel BC, Davies DR Proc Natl Acad Sci. USA (1987) 84:8075–8079
Skerra A, Pluckthun A Science (1988)240:1038–1040
Towbin H, Staehelin T, Gordon J Proc Natl Acad Sci USA (1979) 76:4350–4354.
Utsumi S, Karush F, Biochemistry (1964)3:1329–1338
Ward ES, Gussow DH, Griffiths A, Jones PT, Winter G (1989) submitted.
Verhoeyen M, Milstein C, Winter G Science (1988) 239:1534–1536
Yanisch-Perron C, Vieira J, Messing J Gene (1985) 33:103–119.
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Ward, E.S., Gussow, D.H., Griffiths, A., Jones, P.T., Winter, G.P. (1989). Expression and Secretion of Repertoires of VH Domains in Escherichia Coli: Isolation of Antigen Binding Activities. In: Melchers, F., et al. Progress in Immunology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-83755-5_153
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DOI: https://doi.org/10.1007/978-3-642-83755-5_153
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