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
. 1985 Oct;82(20):7048–7052. doi: 10.1073/pnas.82.20.7048

T-cell antigenic sites tend to be amphipathic structures.

C DeLisi, J A Berzofsky
PMCID: PMC391307  PMID: 2413457

Abstract

We propose, on the basis of physical chemical and biological requirements for T-cell activation by antigen, that sites on a protein that can stimulate T lymphocytes will be capable of forming a stable amphipathic structure (i.e., one with separated hydrophobic and hydrophilic surfaces), displaying periodicity in hydrophobic residues. A spectral analysis of the 12 antigenic sites to which the method could be applied indicates that the amphipathic periodicity hypothesis is valid for 10 of them, generally with reliabilities that are well above 98%, with periodicities compatible with an alpha-helical structure. An 11th case manifests a different type of amphipathicity. The analyses require only a knowledge of amino acid sequence. The finding that T-cell antigenic sites show a high correlation with amphipathicity greatly simplifies the search for such sites and is potentially important for vaccine development.

Full text

PDF
7048

Selected References

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

  1. Allen P. M., Matsueda G. R., Haber E., Unanue E. R. Specificity of the T cell receptor: two different determinants are generated by the same peptide and the I-Ak molecule. J Immunol. 1985 Jul;135(1):368–373. [PubMed] [Google Scholar]
  2. Allen P. M., Strydom D. J., Unanue E. R. Processing of lysozyme by macrophages: identification of the determinant recognized by two T-cell hybridomas. Proc Natl Acad Sci U S A. 1984 Apr;81(8):2489–2493. doi: 10.1073/pnas.81.8.2489. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Benacerraf B. A hypothesis to relate the specificity of T lymphocytes and the activity of I region-specific Ir genes in macrophages and B lymphocytes. J Immunol. 1978 Jun;120(6):1809–1812. [PubMed] [Google Scholar]
  4. Benjamin D. C., Berzofsky J. A., East I. J., Gurd F. R., Hannum C., Leach S. J., Margoliash E., Michael J. G., Miller A., Prager E. M. The antigenic structure of proteins: a reappraisal. Annu Rev Immunol. 1984;2:67–101. doi: 10.1146/annurev.iy.02.040184.000435. [DOI] [PubMed] [Google Scholar]
  5. Berkower I., Buckenmeyer G. K., Gurd F. R., Berzofsky J. A. A possible immunodominant epitope recognized by murine T lymphocytes immune to different myoglobins. Proc Natl Acad Sci U S A. 1982 Aug;79(15):4723–4727. doi: 10.1073/pnas.79.15.4723. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Berkower I., Kawamura H., Matis L. A., Berzofsky J. A. T cell clones to two major T cell epitopes of myoglobin: effect of I-A/I-E restriction on epitope dominance. J Immunol. 1985 Oct;135(4):2628–2634. [PubMed] [Google Scholar]
  7. Berkower I., Matis L. A., Buckenmeyer G. K., Gurd F. R., Longo D. L., Berzofsky J. A. Identification of distinct predominant epitopes recognized by myoglobin-specific T cells under the control of different Ir genes and characterization of representative T cell clones. J Immunol. 1984 Mar;132(3):1370–1378. [PubMed] [Google Scholar]
  8. Berzofsky J. A. Intrinsic and extrinsic factors in protein antigenic structure. Science. 1985 Sep 6;229(4717):932–940. doi: 10.1126/science.2410982. [DOI] [PubMed] [Google Scholar]
  9. Eisenberg D., Weiss R. M., Terwilliger T. C. The hydrophobic moment detects periodicity in protein hydrophobicity. Proc Natl Acad Sci U S A. 1984 Jan;81(1):140–144. doi: 10.1073/pnas.81.1.140. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Finer-Moore J., Stroud R. M. Amphipathic analysis and possible formation of the ion channel in an acetylcholine receptor. Proc Natl Acad Sci U S A. 1984 Jan;81(1):155–159. doi: 10.1073/pnas.81.1.155. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. GELL P. G., BENACERRAF B. Studies on hypersensitivity. II. Delayed hypersensitivity to denatured proteins in guinea pigs. Immunology. 1959 Jan;2(1):64–70. [PMC free article] [PubMed] [Google Scholar]
  12. Godfrey W. L., Lewis G. K., Goodman J. W. The anatomy of an antigen molecule: functional subregions of L-tyrosine-p-azobenzenearsonate. Mol Immunol. 1984 Oct;21(10):969–978. doi: 10.1016/0161-5890(84)90155-x. [DOI] [PubMed] [Google Scholar]
  13. Hackett C. J., Dietzschold B., Gerhard W., Ghrist B., Knorr R., Gillessen D., Melchers F. Influenza virus site recognized by a murine helper T cell specific for H1 strains. Localization to a nine amino acid sequence in the hemagglutinin molecule. J Exp Med. 1983 Aug 1;158(2):294–302. doi: 10.1084/jem.158.2.294. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hansburg D., Fairwell T., Schwartz R. H., Appella E. The T lymphocyte response to cytochrome c. IV. Distinguishable sites on a peptide antigen which affect antigenic strength and memory. J Immunol. 1983 Jul;131(1):319–324. [PubMed] [Google Scholar]
  15. Hopp T. P., Woods K. R. Prediction of protein antigenic determinants from amino acid sequences. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3824–3828. doi: 10.1073/pnas.78.6.3824. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hurwitz J. L., Herber-Katz E., Hackett C. J., Gerhard W. Characterization of the murine TH response to influenza virus hemagglutinin: evidence for three major specificities. J Immunol. 1984 Dec;133(6):3371–3377. [PubMed] [Google Scholar]
  17. Kaiser E. T., Kézdy F. J. Amphiphilic secondary structure: design of peptide hormones. Science. 1984 Jan 20;223(4633):249–255. doi: 10.1126/science.6322295. [DOI] [PubMed] [Google Scholar]
  18. Katz M. E., Maizels R. M., Wicker L., Miller A., Sercarz E. E. Immunological focusing by th mouse major histocompatibility complex: mouse strains confronted with distantly related lysozymes confine their attention to very few epitopes. Eur J Immunol. 1982 Jul;12(7):535–540. doi: 10.1002/eji.1830120702. [DOI] [PubMed] [Google Scholar]
  19. Klein P., Kanehisa M., DeLisi C. Prediction of protein function from sequence properties. Discriminant analysis of a data base. Biochim Biophys Acta. 1984 Jun 28;787(3):221–226. doi: 10.1016/0167-4838(84)90312-1. [DOI] [PubMed] [Google Scholar]
  20. Kyte J., Doolittle R. F. A simple method for displaying the hydropathic character of a protein. J Mol Biol. 1982 May 5;157(1):105–132. doi: 10.1016/0022-2836(82)90515-0. [DOI] [PubMed] [Google Scholar]
  21. Lamb J. R., Eckels D. D., Lake P., Woody J. N., Green N. Human T-cell clones recognize chemically synthesized peptides of influenza haemagglutinin. Nature. 1982 Nov 4;300(5887):66–69. doi: 10.1038/300066a0. [DOI] [PubMed] [Google Scholar]
  22. Lerner R. A. Antibodies of predetermined specificity in biology and medicine. Adv Immunol. 1984;36:1–44. doi: 10.1016/s0065-2776(08)60898-6. [DOI] [PubMed] [Google Scholar]
  23. Manca F., Clarke J. A., Miller A., Sercarz E. E., Shastri N. A limited region within hen egg-white lysozyme serves as the focus for a diversity of T cell clones. J Immunol. 1984 Oct;133(4):2075–2078. [PubMed] [Google Scholar]
  25. Pincus M. R., Gerewitz F., Schwartz R. H., Scheraga H. A. Correlation between the conformation of cytochrome c peptides and their stimulatory activity in a T-lymphocyte proliferation assay. Proc Natl Acad Sci U S A. 1983 Jun;80(11):3297–3300. doi: 10.1073/pnas.80.11.3297. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Rosenthal A. S. Determinant selection and macrophage function in genetic control of the immune response. Immunol Rev. 1978;40:136–152. doi: 10.1111/j.1600-065x.1978.tb00404.x. [DOI] [PubMed] [Google Scholar]
  27. Shimonkevitz R., Colon S., Kappler J. W., Marrack P., Grey H. M. Antigen recognition by H-2-restricted T cells. II. A tryptic ovalbumin peptide that substitutes for processed antigen. J Immunol. 1984 Oct;133(4):2067–2074. [PubMed] [Google Scholar]
  28. Streicher H. Z., Berkower I. J., Busch M., Gurd F. R., Berzofsky J. A. Antigen conformation determines processing requirements for T-cell activation. Proc Natl Acad Sci U S A. 1984 Nov;81(21):6831–6835. doi: 10.1073/pnas.81.21.6831. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Tainer J. A., Getzoff E. D., Alexander H., Houghten R. A., Olson A. J., Lerner R. A., Hendrickson W. A. The reactivity of anti-peptide antibodies is a function of the atomic mobility of sites in a protein. Nature. 1984 Nov 8;312(5990):127–134. doi: 10.1038/312127a0. [DOI] [PubMed] [Google Scholar]
  30. Takano T. Structure of myoglobin refined at 2-0 A resolution. I. Crystallographic refinement of metmyoglobin from sperm whale. J Mol Biol. 1977 Mar 5;110(3):537–568. doi: 10.1016/s0022-2836(77)80111-3. [DOI] [PubMed] [Google Scholar]
  31. Thomas J. W., Danho W., Bullesbach E., Föhles J., Rosenthal A. S. Immune response gene control of determinant selection. III. Polypeptide fragments of insulin are differentially recognized by T but not by B cells in insulin immune guinea pigs. J Immunol. 1981 Mar;126(3):1095–1100. [PubMed] [Google Scholar]
  32. Unanue E. R. Antigen-presenting function of the macrophage. Annu Rev Immunol. 1984;2:395–428. doi: 10.1146/annurev.iy.02.040184.002143. [DOI] [PubMed] [Google Scholar]
  33. Watts T. H., Gariépy J., Schoolnik G. K., McConnell H. M. T-cell activation by peptide antigen: effect of peptide sequence and method of antigen presentation. Proc Natl Acad Sci U S A. 1985 Aug;82(16):5480–5484. doi: 10.1073/pnas.82.16.5480. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Westhof E., Altschuh D., Moras D., Bloomer A. C., Mondragon A., Klug A., Van Regenmortel M. H. Correlation between segmental mobility and the location of antigenic determinants in proteins. Nature. 1984 Sep 13;311(5982):123–126. doi: 10.1038/311123a0. [DOI] [PubMed] [Google Scholar]
  35. Wilson I. A., Skehel J. J., Wiley D. C. Structure of the haemagglutinin membrane glycoprotein of influenza virus at 3 A resolution. Nature. 1981 Jan 29;289(5796):366–373. doi: 10.1038/289366a0. [DOI] [PubMed] [Google Scholar]
  36. Ziegler K., Unanue E. R. Identification of a macrophage antigen-processing event required for I-region-restricted antigen presentation to T lymphocytes. J Immunol. 1981 Nov;127(5):1869–1875. [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