Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1992 Apr 15;89(8):3175–3179. doi: 10.1073/pnas.89.8.3175

Human combinatorial antibody libraries to hepatitis B surface antigen.

S L Zebedee 1, C F Barbas 3rd 1, Y L Hom 1, R H Caothien 1, R Graff 1, J DeGraw 1, J Pyati 1, R LaPolla 1, D R Burton 1, R A Lerner 1, et al.
PMCID: PMC48828  PMID: 1373487

Abstract

Human antibody Fab fragments that bind to hepatitis B surface antigen (HBsAg) were generated by using a recombinant phage surface-display expression system. Characterization of HBsAg-specific Fab fragments isolated from two vaccinated individuals reveals diversity in specificity of antigen binding and in the sequences of the complementarity-determining region. The sequence results show examples of human light-chain promiscuity that result in fine specificity changes and a strong relationship to a human germ-line gene. This application illustrates further that this technique is a powerful tool to isolate distinct human antibodies against immunogenic viral targets.

Full text

PDF
3179

Images in this article

3177Image
on p.3177
3177Image
on p.3177

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ames G. F., Prody C., Kustu S. Simple, rapid, and quantitative release of periplasmic proteins by chloroform. J Bacteriol. 1984 Dec;160(3):1181–1183. doi: 10.1128/jb.160.3.1181-1183.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barbas C. F., 3rd, Kang A. S., Lerner R. A., Benkovic S. J. Assembly of combinatorial antibody libraries on phage surfaces: the gene III site. Proc Natl Acad Sci U S A. 1991 Sep 15;88(18):7978–7982. doi: 10.1073/pnas.88.18.7978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bass S., Greene R., Wells J. A. Hormone phage: an enrichment method for variant proteins with altered binding properties. Proteins. 1990;8(4):309–314. doi: 10.1002/prot.340080405. [DOI] [PubMed] [Google Scholar]
  4. Burton D. R., Barbas C. F., 3rd, Persson M. A., Koenig S., Chanock R. M., Lerner R. A. A large array of human monoclonal antibodies to type 1 human immunodeficiency virus from combinatorial libraries of asymptomatic seropositive individuals. Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10134–10137. doi: 10.1073/pnas.88.22.10134. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Caton A. J., Koprowski H. Influenza virus hemagglutinin-specific antibodies isolated from a combinatorial expression library are closely related to the immune response of the donor. Proc Natl Acad Sci U S A. 1990 Aug;87(16):6450–6454. doi: 10.1073/pnas.87.16.6450. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chang C. N., Model P., Blobel G. Membrane biogenesis: cotranslational integration of the bacteriophage f1 coat protein into an Escherichia coli membrane fraction. Proc Natl Acad Sci U S A. 1979 Mar;76(3):1251–1255. doi: 10.1073/pnas.76.3.1251. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Clackson T., Hoogenboom H. R., Griffiths A. D., Winter G. Making antibody fragments using phage display libraries. Nature. 1991 Aug 15;352(6336):624–628. doi: 10.1038/352624a0. [DOI] [PubMed] [Google Scholar]
  8. Crissman J. W., Smith G. P. Gene-III protein of filamentous phages: evidence for a carboxyl-terminal domain with a role in morphogenesis. Virology. 1984 Jan 30;132(2):445–455. doi: 10.1016/0042-6822(84)90049-7. [DOI] [PubMed] [Google Scholar]
  9. Cwirla S. E., Peters E. A., Barrett R. W., Dower W. J. Peptides on phage: a vast library of peptides for identifying ligands. Proc Natl Acad Sci U S A. 1990 Aug;87(16):6378–6382. doi: 10.1073/pnas.87.16.6378. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Devlin J. J., Panganiban L. C., Devlin P. E. Random peptide libraries: a source of specific protein binding molecules. Science. 1990 Jul 27;249(4967):404–406. doi: 10.1126/science.2143033. [DOI] [PubMed] [Google Scholar]
  11. Hay F. C., Soltys A. J., Tribbick G., Geysen H. M. Framework peptides from kappa IIIb rheumatoid factor light chains with binding activity for aggregated IgG. Eur J Immunol. 1991 Aug;21(8):1837–1841. doi: 10.1002/eji.1830210809. [DOI] [PubMed] [Google Scholar]
  12. Helfman D. M., Feramisco J. R., Fiddes J. C., Thomas G. P., Hughes S. H. Identification of clones that encode chicken tropomyosin by direct immunological screening of a cDNA expression library. Proc Natl Acad Sci U S A. 1983 Jan;80(1):31–35. doi: 10.1073/pnas.80.1.31. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hoogenboom H. R., Griffiths A. D., Johnson K. S., Chiswell D. J., Hudson P., Winter G. Multi-subunit proteins on the surface of filamentous phage: methodologies for displaying antibody (Fab) heavy and light chains. Nucleic Acids Res. 1991 Aug 11;19(15):4133–4137. doi: 10.1093/nar/19.15.4133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Huse W. D., Sastry L., Iverson S. A., Kang A. S., Alting-Mees M., Burton D. R., Benkovic S. J., Lerner R. A. Generation of a large combinatorial library of the immunoglobulin repertoire in phage lambda. Science. 1989 Dec 8;246(4935):1275–1281. doi: 10.1126/science.2531466. [DOI] [PubMed] [Google Scholar]
  15. Kabat E. A., Wu T. T. Identical V region amino acid sequences and segments of sequences in antibodies of different specificities. Relative contributions of VH and VL genes, minigenes, and complementarity-determining regions to binding of antibody-combining sites. J Immunol. 1991 Sep 1;147(5):1709–1719. [PubMed] [Google Scholar]
  16. Kang A. S., Barbas C. F., Janda K. D., Benkovic S. J., Lerner R. A. Linkage of recognition and replication functions by assembling combinatorial antibody Fab libraries along phage surfaces. Proc Natl Acad Sci U S A. 1991 May 15;88(10):4363–4366. doi: 10.1073/pnas.88.10.4363. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kang A. S., Jones T. M., Burton D. R. Antibody redesign by chain shuffling from random combinatorial immunoglobulin libraries. Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11120–11123. doi: 10.1073/pnas.88.24.11120. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kipps T. J., Tomhave E., Chen P. P., Carson D. A. Autoantibody-associated kappa light chain variable region gene expressed in chronic lymphocytic leukemia with little or no somatic mutation. Implications for etiology and immunotherapy. J Exp Med. 1988 Mar 1;167(3):840–852. doi: 10.1084/jem.167.3.840. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kipps T. J., Tomhave E., Chen P. P., Fox R. I. Molecular characterization of a major autoantibody-associated cross-reactive idiotype in Sjogren's syndrome. J Immunol. 1989 Jun 15;142(12):4261–4268. [PubMed] [Google Scholar]
  20. Lowman H. B., Bass S. H., Simpson N., Wells J. A. Selecting high-affinity binding proteins by monovalent phage display. Biochemistry. 1991 Nov 12;30(45):10832–10838. doi: 10.1021/bi00109a004. [DOI] [PubMed] [Google Scholar]
  21. Mullinax R. L., Gross E. A., Amberg J. R., Hay B. N., Hogrefe H. H., Kubitz M. M., Greener A., Alting-Mees M., Ardourel D., Short J. M. Identification of human antibody fragment clones specific for tetanus toxoid in a bacteriophage lambda immunoexpression library. Proc Natl Acad Sci U S A. 1990 Oct;87(20):8095–8099. doi: 10.1073/pnas.87.20.8095. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Newkirk M. M., Gram H., Heinrich G. F., Ostberg L., Capra J. D., Wasserman R. L. Complete protein sequences of the variable regions of the cloned heavy and light chains of a human anti-cytomegalovirus antibody reveal a striking similarity to human monoclonal rheumatoid factors of the Wa idiotypic family. J Clin Invest. 1988 May;81(5):1511–1518. doi: 10.1172/JCI113483. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Parmley S. F., Smith G. P. Antibody-selectable filamentous fd phage vectors: affinity purification of target genes. Gene. 1988 Dec 20;73(2):305–318. doi: 10.1016/0378-1119(88)90495-7. [DOI] [PubMed] [Google Scholar]
  24. Persson M. A., Caothien R. H., Burton D. R. Generation of diverse high-affinity human monoclonal antibodies by repertoire cloning. Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2432–2436. doi: 10.1073/pnas.88.6.2432. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Radoux V., Chen P. P., Sorge J. A., Carson D. A. A conserved human germline V kappa gene directly encodes rheumatoid factor light chains. J Exp Med. 1986 Dec 1;164(6):2119–2124. doi: 10.1084/jem.164.6.2119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Sanz I. Multiple mechanisms participate in the generation of diversity of human H chain CDR3 regions. J Immunol. 1991 Sep 1;147(5):1720–1729. [PubMed] [Google Scholar]
  27. Sastry L., Alting-Mees M., Huse W. D., Short J. M., Sorge J. A., Hay B. N., Janda K. D., Benkovic S. J., Lerner R. A. Cloning of the immunological repertoire in Escherichia coli for generation of monoclonal catalytic antibodies: construction of a heavy chain variable region-specific cDNA library. Proc Natl Acad Sci U S A. 1989 Aug;86(15):5728–5732. doi: 10.1073/pnas.86.15.5728. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Scott J. K., Smith G. P. Searching for peptide ligands with an epitope library. Science. 1990 Jul 27;249(4967):386–390. doi: 10.1126/science.1696028. [DOI] [PubMed] [Google Scholar]
  29. Seeff L. B., Wright E. C., Zimmerman H. J., Alter H. J., Dietz A. A., Felsher B. F., Finkelstein J. D., Garcia-Pont P., Gerin J. L., Greenlee H. B. Type B hepatitis after needle-stick exposure: prevention with hepatitis B immune globulin. Final report of the Veterans Administration Cooperative Study. Ann Intern Med. 1978 Mar;88(3):285–293. doi: 10.7326/0003-4819-88-3-285. [DOI] [PubMed] [Google Scholar]
  30. Smith G. P. Filamentous fusion phage: novel expression vectors that display cloned antigens on the virion surface. Science. 1985 Jun 14;228(4705):1315–1317. doi: 10.1126/science.4001944. [DOI] [PubMed] [Google Scholar]
  31. Williamson R. A., Persson M. A., Burton D. R. Expression of a human monoclonal anti-(rhesus D) Fab fragment in Escherichia coli with the use of bacteriophage lambda vectors. Biochem J. 1991 Jul 15;277(Pt 2):561–563. doi: 10.1042/bj2770561. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Zebedee S. L., Lamb R. A. Influenza A virus M2 protein: monoclonal antibody restriction of virus growth and detection of M2 in virions. J Virol. 1988 Aug;62(8):2762–2772. doi: 10.1128/jvi.62.8.2762-2772.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES