Review
Full Access
From the Structure of Antibodies to the Diversification of the Immune Responce (Noble Lecture)†
Dr. Cesar Milstein,
Dr. Cesar Milstein
Laboratory of Molecular Biology, Medical Research Council Center, Hills Road, Cambridge CB2 2QH (England)
Search for more papers by this authorDr. Cesar Milstein,
Dr. Cesar Milstein
Laboratory of Molecular Biology, Medical Research Council Center, Hills Road, Cambridge CB2 2QH (England)
Search for more papers by this author†
Copyright © The Nobel Foundation 1985.—We thank the Nobel Foundation, Stockholm, for permission to publish this article.
Abstract
The unimaginable variety of antibody structures is evidenced by the fact that an animal produces specific antibodies against bacteria, viruses, and other foreign substances, even against substances with which it has had no prior contact. How is this possible? In his lecture, on the occasion of accepting the 1984 Nobel Prize for Physiology and Medicine, Cesar Milstein describes work directed toward answering this question. These investigations have led to, among other things, the development of the hybridoma technique in collaboration with G. Köhler.
References
- 1(a)
G. M. Edelman,
Angew. Chem.
85 (1973) 1083–1097;
10.1002/ange.19730852404 Google Scholar(b) R. R. Porter, Angew. Chem. 85 (1973) 1097–1101.
- 2 C. Milstein, J. Mol. Biol. 9 (1964) 836.
- 3 C. Milstein, Biochem. J. 101 (1966) 352–368.
- 4 N. Hilschmann, L. C. Craig, Proc. Natl. Acad. Sci. USA 53 (1965) 1403–1409.
- 5(a) B. Frangione, C. Milstein, J. R. L. Pink, Nature London 221 (1969) 145–148; (b) J. Svasti, C. Milstein, Nature London 228 (1970) 930–935.
- 6 W. J. Dreyer, C. J. Bennet, Proc. Natl. Acad. Sci. USA 54 (1965) 864–869.
- 7 S. Brenner, C. Milstein, Nature London 211 (1966) 242–243.
- 8 O. Smithies, Science 157 (1967) 267–273.
- 9 C. Milstein, Nature London 216 (1967) 330–332.
- 10 C. Milstein, C. P. Milstein, A. Feinstein, Nature London 221 (1969) 151–154.
- 11 T. T. Wu, E. A. Kabat, J. Exp. Med. 132 (1970) 211–250.
- 12 Review: L. M. Amzel, R. S. Poljak, Annu. Rev. Biochem. 48 (1979) 961–997.
- 13 C. Milstein, J. R. L. Pink, Progr. Biphys. Mol. Biol. 21 (1970) 209–263.
- 14 M. Potter, Physiol. Rev. 52 (1972) 631–719.
- 15 K. Horibata, A. W. Harris, Exp. Cell Res. 60 (1970) 61–70.
- 16 J. Stavnezer, R.-C. C. Huang, Nature London New Biol. 230 (1971) 172.
- 17 C. Milstein, G. G. Brownlee, T. M. Harrison, M. B. Mathews, Nature London New Biol. 239 (1972) 117–120.
- 18 T. M. Harrison, G. G. Brownlee, C. Milstein, Eur. J. Biochem. 47 (1974) 613–620.
- 19 G. G. Brownlee, E. M. Cartwright, N. J. Cowan, J. M. Jarvis, C. Milstein, Nature London 244 (1973) 236–240.
- 20 C. Milstein, G. G. Brownlee, E. M. Cartwright, J. M. Jarvis, N. J. Proudfoot, Nature London 252 (1974) 354–359.
- 21 P. H. Hamlyn, M. J. Gait, C. Milstein, Nucleic Acids Res. 9 (1981) 4485–4494.
- 22 R. G. H. Cotton, D. S. Secher, C. Milstein, Eur. J. Immunol. 3 (1973) 136–140.
- 23 K. Adetugbo, C. Milstein, D. S. Secher, Nature London 265 (1977) 299–304.
- 24 D. S. Secher, C. Milstein, K. Adetugbo, Immunol. Rev. 36 (1977) 51–72.
- 25 R. G. H. Cotton, C. Milstein, Nature London 244 (1973) 42–43.
- 26 S. Rudikoff, A. M. Giusti, W. D. Cook, M. D. Scharff, Proc. Natl. Acad. Sci. USA 79 (1982) 1979–1983.
- 27 G. Galfre, S. C. Howe, C. Milstein, G. W. Butcher, J. C. Howard, Nature London 266 (1977) 550–552.
- 28 T. Pearson, G. Galfre, A. Ziegler, C. Milstein, Eur. J. Immunol. 7 (1977) 684–690.
- 29 A. F. Williams, G. Galfre, C. Milstein, Cell 12 (1977) 663–673.
- 30 P. L. Stern, K. R. Willison, E. S. Lennox, G. Galfre, C. Milstein, D. S. Secher, A. Ziegler, Cell 14 (1978) 775–783.
- 31
C. Milstein,
G. Galfre,
D. S. Secher,
T. Springer,
Ciba Found. Symp. 66;
(“ Human Biology: Possibilities and Realities”)
Excerpta Medica: Amsterdam
1979. p. 251–266.
10.1002/9780470720486.ch11 Google Scholar
- 32 A. C. Cuello, G. Galfre, C. Milstein, Proc. Natl. Acad. Sci. USA 76 (1979) 3532–3536.
- 33 D. Voak, S. Sacks, T. Alderson, F. Takei, E. S. Lennox, J. M. Jarvis, C. Milstein, J. Darnborough, Vox Sang. 39 (1980) 134–140.
- 34 D. S. Secher, D. C. Burke, Nature London 285 (1980) 446–450.
- 35 G. Galfre, C. Milstein, B. W. Wright, Nature London 277 (1979) 131–133.
- 36 C. Milstein, A. C. Cuello, Nature London 305 (1983) 537–540.
- 37 T. H. Rabbitts, C. Milstein, Contemp. Top. Mol. Immunol. 6 (1977) 117–143.
- 38 S. Tonegawa, N. Hozumi, G. Matthyssens, R. Schuller, Cold Spring Harbor Symp. Quant. Biol. 41 (1976) 877–889.
- 39 Cold Spring Harbor Symp. Quant. Biol. 41 (1976).
- 40Review: S. Tonegawa, Nature London 302 (1983) 571–581.
- 41 G. M. Edelman, J. A. Gally, Proc. Natl. Acad. Sci. USA 57 (1967) 353–358.
- 42 E. A. Kabat, T. T. Wu, H. Bilofsky, Proc. Natl. Acad. Sci. USA 75 (1978) 2429–2433.
- 43 F. W. Alt, D. Baltimore, Proc. Natl. Acad. Sci. USA 79 (1982) 4118–4122.
- 44 M. Cohn, Ann. N. Y. Acad. Sci. 190 (1971) 529.
- 45 N. K. Jerne, Eur, J. Immunol. 1 (1971) 1–9.
- 46 F. Haurowitz, Cold Spring Harbor Symp. Quant. Biol. 32 (1967) 559–567.
- 47 E. Westhof, D. Altschuh, D. Moras, A. C. Bloomer, A. Mondragon, A. Klug, M. H. V. Van Regenmortel, Nature London 311 (1984) 123–127.
- 48 J. A. Tainer, E. D. Getsoff, H. Alexander, R. A. Houghton, A. J. Olson, R. A. Lerner, W. A. Hendrickson, Nature London 312 (1984) 127–134.
- 49 See, for example: H. Waldmann, C. Milstein in P. J. Lachmann, D. K. Peters (Eds.): Clinical Aspects of Immunology, Vol. 1, 4th ed., Blackwells Scientific Publications, Oxford 1982, p. 476–503.
- 50 M. Kaartinen, G. M. Griffiths, P. H. Hamlyn, A. F. Markham, K. Karjalainen, J. L. T. Pelkonen, O. Mäkelä, C. Milstein, J. Immunol. 130 (1983) 937–945.
- 51 G. M. Griffiths, C. Berek, M. Kaartinen, C. Milstein, Nature London 312 (1984) 271–275.
- 52 J. L. Preud'homme, B. K. Birshtein, M. D. Scharff, Proc. Natl. Acad. Sci. USA 72 (1975) 1427–1430.
- 53 C. Milstein, Proc. R. Soc. London B 211 (1981) 393–412 (Wellcome Foundation Lecture).
- 54 M. S. Neuberger, G. T. Williams, E. B. Mitchell, S. S. Jouhal, J. G. Flanagan, T. H. Rabbitts, Nature London 314 (1985) 268–270.
- 55 M. S. Neuberger, G. T. Williams, R. O. Fox, Nature London 312 (1984) 604–608.
- 56 G. Köhler, C. Milstein, Nature London 256 (1975) 495–497.
- 57 W. Szybalski, E. H. Szybalska, G. Ragni, Natl. cancer Inst. Monogr. 7 (1962) 75–89.
- 58 G. Galfré, C. Milstein, Methods Enzymol. 73 (1981) 3–46.
- 59 M. Kaartinen, G. M. Griffiths, A. F. Markham, C. Milstein, Nature London 304 (1983) 320–324.
- 60 J. C. Howard, G. W. Butcher, G. Galfrée, C. Milstein, C. P. Milstein, Immunol, Rev. 47 (1979) 139–174.
- 61 T. Pearson, G. Galfré, A. Ziegler, C. Milstein, Eur, J. Immunol. 7 (1977) 684–690.
- 62 C. J. Barnstable, W. F. Bodmer, G. Brown, G. Galfré, C. Milstein, A. F. Williams, A. Ziegler, Cell 14 (1978) 9–20.
- 63 T. Springer, G. Galfré, D. S. Secher, C. Milstein, Eur. J. Immunol. 8 (1978) 539–551.
- 64 T. Springer, G. Galfré, D. S. Secher, C. Milstein, Eur, J. Immunol. 9 (1979) 301–306.
- 65 F. Takei, H. Waldmann, E. S. Lennox, C. Milstein, Eur. J. Immunol. 10 (1980) 503–509.
- 66 A. J. McMichael, J. R. Pilch, G. Galfré, D. Y. Mason, J. W. Fabre, C. Milstein, Eur. J. Immunol. 9 (1979) 206–210.
- 67 A. C. Cuello, J. V. Priestly, C. Milstein, Proc. Natl. Acad. Sci. USA 79 (1982) 665–669.
- 68 D. Voak, E. S. Lennox, S. Sacks, C. Milstein, J. Darnborough, Med. Lab. Sci. 39 (1982) 109–122.
