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
. 1981 Jun;78(6):3824–3828. doi: 10.1073/pnas.78.6.3824

Prediction of protein antigenic determinants from amino acid sequences.

T P Hopp, K R Woods
PMCID: PMC319665  PMID: 6167991

Abstract

A method is presented for locating protein antigenic determinants by analyzing amino acid sequences in order to find the point of greatest local hydrophilicity. This is accomplished by assigning each amino acid a numerical value (hydrophilicity value) and then repetitively averaging these values along the peptide chain. The point of highest local average hydrophilicity is invariably located in, or immediately adjacent to, an antigenic determinant. It was found that the prediction success rate depended on averaging group length, with hexapeptide averages yielding optimal results. The method was developed using 12 proteins for which extensive immunochemical analysis has been carried out and subsequently was used to predict antigenic determinants for the following proteins: hepatitis B surface antigen, influenza hemagglutinins, fowl plague virus hemagglutinin, human histocompatibility antigen HLA-B7, human interferons, Escherichia coli and cholera enterotoxins, ragweed allergens Ra3 and Ra5, and streptococcal M protein. The hepatitis B surface antigen sequence was synthesized by chemical means and was shown to have antigenic activity by radioimmunoassay.

Full text

PDF
3827

Selected References

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

  1. ANDERER F. A. VERSUCHE ZUR BESTIMMUNG DER SEROLOGISCH DETERMINANTEN GRUPPEN DES TABAKMOSAIKVIRUS. Z Naturforsch B. 1963 Dec;18:1010–1014. [PubMed] [Google Scholar]
  2. Arnon R., Sela M., Parant M., Chedid L. Antiviral response elicited by a completely synthetic antigen with built-in adjuvanticity. Proc Natl Acad Sci U S A. 1980 Nov;77(11):6769–6772. doi: 10.1073/pnas.77.11.6769. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Atassi M. Z. Antigenic structure of myoglobin: the complete immunochemical anatomy of a protein and conclusions relating to antigenic structures of proteins. Immunochemistry. 1975 May;12(5):423–438. doi: 10.1016/0019-2791(75)90010-5. [DOI] [PubMed] [Google Scholar]
  4. Atassi M. Z., Lee C. L. The precise and entire antigenic structure of native lysozyme. Biochem J. 1978 May 1;171(2):429–434. doi: 10.1042/bj1710429. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Beachey E. H., Seyer J. M., Kang A. H. Primary structure of protective antigens of type 24 streptococcal M protein. J Biol Chem. 1980 Jul 10;255(13):6284–6289. [PubMed] [Google Scholar]
  6. Chou P. Y., Fasman G. D. Conformational parameters for amino acids in helical, beta-sheet, and random coil regions calculated from proteins. Biochemistry. 1974 Jan 15;13(2):211–222. doi: 10.1021/bi00699a001. [DOI] [PubMed] [Google Scholar]
  7. Dallas W. S., Falkow S. Amino acid sequence homology between cholera toxin and Escherichia coli heat-labile toxin. Nature. 1980 Dec 4;288(5790):499–501. doi: 10.1038/288499a0. [DOI] [PubMed] [Google Scholar]
  8. De L Milton R. C., van Regenmortel M. H. Immunochemical studies of tobacco mosaic virus--III. Demonstration of five antigenic regions in the protein sub-unit. Mol Immunol. 1979 Mar;16(3):179–184. doi: 10.1016/0161-5890(79)90143-3. [DOI] [PubMed] [Google Scholar]
  9. Derynck R., Content J., DeClercq E., Volckaert G., Tavernier J., Devos R., Fiers W. Isolation and structure of a human fibroblast interferon gene. Nature. 1980 Jun 19;285(5766):542–547. doi: 10.1038/285542a0. [DOI] [PubMed] [Google Scholar]
  10. Eylar E. H. Peptides and autoimmune disease. Adv Exp Med Biol. 1978;98:259–281. doi: 10.1007/978-1-4615-8858-0_14. [DOI] [PubMed] [Google Scholar]
  11. Garoff H., Frischauf A. M., Simons K., Lehrach H., Delius H. Nucleotide sequence of cdna coding for Semliki Forest virus membrane glycoproteins. Nature. 1980 Nov 20;288(5788):236–241. doi: 10.1038/288236a0. [DOI] [PubMed] [Google Scholar]
  12. Goeddel D. V., Yelverton E., Ullrich A., Heyneker H. L., Miozzari G., Holmes W., Seeburg P. H., Dull T., May L., Stebbing N. Human leukocyte interferon produced by E. coli is biologically active. Nature. 1980 Oct 2;287(5781):411–416. doi: 10.1038/287411a0. [DOI] [PubMed] [Google Scholar]
  13. Hurrell J. G., Smith J. A., Leach S. J. The detection of five antigenically reactive regions in the soybean leghemoglobin a molecule. Immunochemistry. 1978 May;15(5):297–302. doi: 10.1016/0161-5890(78)90089-5. [DOI] [PubMed] [Google Scholar]
  14. Jemmerson R., Margoliash E. Topographic antigenic determinants on cytochrome c. Immunoadsorbent separation of the rabbit antibody populations directed against horse cytochrome. J Biol Chem. 1979 Dec 25;254(24):12706–12716. [PubMed] [Google Scholar]
  15. Jou W. M., Verhoeyen M., Devos R., Saman E., Fang R., Huylebroeck D., Fiers W., Threlfall G., Barber C., Carey N. Complete structure of the hemagglutinin gene from the human influenza A/Victoria/3/75 (H3N2) strain as determined from cloned DNA. Cell. 1980 Mar;19(3):683–696. doi: 10.1016/s0092-8674(80)80045-6. [DOI] [PubMed] [Google Scholar]
  16. Kazim A. L., Atassi M. Z. Prediction and conformation by synthesis of two antigenic sites in human haemoglobin by extrapolation from the known antigenic structure of sperm-whale myoglobin. Biochem J. 1977 Oct 1;167(1):275–278. doi: 10.1042/bj1670275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kelly B., Levy J. G. Immunological studies on the major haptenic peptides from performic acid oxidized ferredoxin from Clostridium pasteurianum. Biochemistry. 1971 May 11;10(10):1763–1766. doi: 10.1021/bi00786a005. [DOI] [PubMed] [Google Scholar]
  18. Klapper D. G., Goodfriend L., Capra J. D. Amino acid sequence of ragweed allergen Ra3. Biochemistry. 1980 Dec 9;19(25):5729–5734. doi: 10.1021/bi00566a010. [DOI] [PubMed] [Google Scholar]
  19. Kurosky A., Markel D. E., Peterson J. W., Fitch W. M. Primary structure of cholera toxin beta-chain: a glycoprotein hormone analog? Science. 1977 Jan 21;195(4275):299–301. doi: 10.1126/science.831277. [DOI] [PubMed] [Google Scholar]
  20. Levitt M. A simplified representation of protein conformations for rapid simulation of protein folding. J Mol Biol. 1976 Jun 14;104(1):59–107. doi: 10.1016/0022-2836(76)90004-8. [DOI] [PubMed] [Google Scholar]
  21. Maxfield F. R., Scheraga H. A. Status of empirical methods for the prediction of protein backbone topography. Biochemistry. 1976 Nov 16;15(23):5138–5153. doi: 10.1021/bi00668a030. [DOI] [PubMed] [Google Scholar]
  22. Mole L. E., Goodfriend L., Lapkoff C. B., Kehoe J. M., Capra J. D. The amino acid sequence of ragweed pollen allergen Ra5. Biochemistry. 1975 Mar 25;14(6):1216–1220. doi: 10.1021/bi00677a019. [DOI] [PubMed] [Google Scholar]
  23. Nozaki Y., Tanford C. The solubility of amino acids and two glycine peptides in aqueous ethanol and dioxane solutions. Establishment of a hydrophobicity scale. J Biol Chem. 1971 Apr 10;246(7):2211–2217. [PubMed] [Google Scholar]
  24. Orr H. T., López de Castro J. A., Lancet D., Strominger J. L. Complete amino acid sequence of a papain-solubilized human histocompatibility antigen, HLA-B7. 2. Sequence determination and search for homologies. Biochemistry. 1979 Dec 11;18(25):5711–5720. doi: 10.1021/bi00592a030. [DOI] [PubMed] [Google Scholar]
  25. Porter A. G., Barber C., Carey N. H., Hallewell R. A., Threlfall G., Emtage J. S. Complete nucleotide sequence of an influenza virus haemagglutinin gene from cloned DNA. Nature. 1979 Nov 29;282(5738):471–477. doi: 10.1038/282471a0. [DOI] [PubMed] [Google Scholar]
  26. Reichlin M. Amino acid substitution and the antigenicity of globular proteins. Adv Immunol. 1975;20:71–123. doi: 10.1016/s0065-2776(08)60207-2. [DOI] [PubMed] [Google Scholar]
  27. Rose G. D., Roy S. Hydrophobic basis of packing in globular proteins. Proc Natl Acad Sci U S A. 1980 Aug;77(8):4643–4647. doi: 10.1073/pnas.77.8.4643. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. So M., McCarthy B. J. Nucleotide sequence of the bacterial transposon Tn1681 encoding a heat-stable (ST) toxin and its identification in enterotoxigenic Escherichia coli strains. Proc Natl Acad Sci U S A. 1980 Jul;77(7):4011–4015. doi: 10.1073/pnas.77.7.4011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Taniguchi T., Mantei N., Schwarzstein M., Nagata S., Muramatsu M., Weissmann C. Human leukocyte and fibroblast interferons are structurally related. Nature. 1980 Jun 19;285(5766):547–549. doi: 10.1038/285547a0. [DOI] [PubMed] [Google Scholar]
  30. Valenzuela P., Gray P., Quiroga M., Zaldivar J., Goodman H. M., Rutter W. J. Nucleotide sequence of the gene coding for the major protein of hepatitis B virus surface antigen. Nature. 1979 Aug 30;280(5725):815–819. doi: 10.1038/280815a0. [DOI] [PubMed] [Google Scholar]
  31. Verhoeyen M., Fang R., Jou W. M., Devos R., Huylebroeck D., Saman E., Fiers W. Antigenic drift between the haemagglutinin of the Hong Kong influenza strains A/Aichi/2/68 and A/Victoria/3/75. Nature. 1980 Aug 21;286(5775):771–776. doi: 10.1038/286771a0. [DOI] [PubMed] [Google Scholar]
  32. Westall F. C., Thompson M. An encephalitogenic region for rabbits. Immunochemistry. 1978 Mar;15(3):189–191. doi: 10.1016/0161-5890(78)90147-5. [DOI] [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