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
. 1993 Mar 1;90(5):1691–1695. doi: 10.1073/pnas.90.5.1691

Predicting the size of the T-cell receptor and antibody combining region from consideration of efficient self-nonself discrimination.

J K Percus 1, O E Percus 1, A S Perelson 1
PMCID: PMC45945  PMID: 7680474

Abstract

The binding of antibody to antigen or T-cell receptor to major histocompatibility complex-peptide complex requires that portions of the two structures have complementary shapes that can closely approach each other. The question that we address here is how large should the complementary regions on the two structures be. The interacting regions are by necessity roughly the same size. To estimate the size (number of contact residues) of an optimal receptor combining region, we assume that the immune system over evolutionary time has been presented with a large random set of foreign molecules that occur on common pathogens, which it must recognize, and a smaller random set of self-antigens to which it must fail to respond. Evolutionarily, the receptors and the molecular groups that the immune system recognizes as epitopes are imagined to have coevolved to maximize the probability that this task is performed. The probability of a receptor matching a random antigen is estimated from this condition. Using a simple model for receptor-ligand interaction, we estimate that the optimal size binding region on immunoglobulin or T-cell receptors will contain about 15 contact residues, in agreement with experimental observation.

Full text

PDF
1691

Selected References

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

  1. Ajitkumar P., Geier S. S., Kesari K. V., Borriello F., Nakagawa M., Bluestone J. A., Saper M. A., Wiley D. C., Nathenson S. G. Evidence that multiple residues on both the alpha-helices of the class I MHC molecule are simultaneously recognized by the T cell receptor. Cell. 1988 Jul 1;54(1):47–56. doi: 10.1016/0092-8674(88)90178-x. [DOI] [PubMed] [Google Scholar]
  2. Amit A. G., Mariuzza R. A., Phillips S. E., Poljak R. J. Three-dimensional structure of an antigen-antibody complex at 2.8 A resolution. Science. 1986 Aug 15;233(4765):747–753. doi: 10.1126/science.2426778. [DOI] [PubMed] [Google Scholar]
  3. Berek C., Milstein C. The dynamic nature of the antibody repertoire. Immunol Rev. 1988 Oct;105:5–26. doi: 10.1111/j.1600-065x.1988.tb00763.x. [DOI] [PubMed] [Google Scholar]
  4. Cancro M. P., Gerhard W., Klinman N. R. The diversity of the influenza-specific primary B-cell repertoire in BALB/c mice. J Exp Med. 1978 Mar 1;147(3):776–787. doi: 10.1084/jem.147.3.776. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Celada F., Seiden P. E. A computer model of cellular interactions in the immune system. Immunol Today. 1992 Feb;13(2):56–62. doi: 10.1016/0167-5699(92)90135-T. [DOI] [PubMed] [Google Scholar]
  6. Chalufour A., Bougueleret L., Claverie J. M., Kourilsky P. Rare sequence motifs are common constituents of hypervariable antibody regions. Ann Inst Pasteur Immunol. 1987 Sep-Oct;138(5):671–685. doi: 10.1016/s0769-2625(87)80023-5. [DOI] [PubMed] [Google Scholar]
  7. Claverie J. M., Kourilsky P., Langlade-Demoyen P., Chalufour-Prochnicka A., Dadaglio G., Tekaia F., Plata F., Bougueleret L. T-immunogenic peptides are constituted of rare sequence patterns. Use in the identification of T epitopes in the human immunodeficiency virus gag protein. Eur J Immunol. 1988 Oct;18(10):1547–1553. doi: 10.1002/eji.1830181012. [DOI] [PubMed] [Google Scholar]
  8. Colman P. M., Laver W. G., Varghese J. N., Baker A. T., Tulloch P. A., Air G. M., Webster R. G. Three-dimensional structure of a complex of antibody with influenza virus neuraminidase. 1987 Mar 26-Apr 1Nature. 326(6111):358–363. doi: 10.1038/326358a0. [DOI] [PubMed] [Google Scholar]
  9. Coutinho A. The self-nonself discrimination and the nature and acquisition of the antibody repertoire. Ann Immunol (Paris) 1980 Nov-Dec;131D(3):235–253. [PubMed] [Google Scholar]
  10. Cygler M., Rose D. R., Bundle D. R. Recognition of a cell-surface oligosaccharide of pathogenic Salmonella by an antibody Fab fragment. Science. 1991 Jul 26;253(5018):442–445. doi: 10.1126/science.1713710. [DOI] [PubMed] [Google Scholar]
  11. Davis M. M., Bjorkman P. J. T-cell antigen receptor genes and T-cell recognition. Nature. 1988 Aug 4;334(6181):395–402. doi: 10.1038/334395a0. [DOI] [PubMed] [Google Scholar]
  12. Jardetzky T. S., Lane W. S., Robinson R. A., Madden D. R., Wiley D. C. Identification of self peptides bound to purified HLA-B27. Nature. 1991 Sep 26;353(6342):326–329. doi: 10.1038/353326a0. [DOI] [PubMed] [Google Scholar]
  13. Karlin S., Bucher P., Brendel V., Altschul S. F. Statistical methods and insights for protein and DNA sequences. Annu Rev Biophys Biophys Chem. 1991;20:175–203. doi: 10.1146/annurev.bb.20.060191.001135. [DOI] [PubMed] [Google Scholar]
  14. Ohno S. Many peptide fragments of alien antigens are homologous with host proteins, thus canalizing T-cell responses. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3065–3068. doi: 10.1073/pnas.88.8.3065. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Perelson A. S. Immune network theory. Immunol Rev. 1989 Aug;110:5–36. doi: 10.1111/j.1600-065x.1989.tb00025.x. [DOI] [PubMed] [Google Scholar]
  16. Perelson A. S., Oster G. F. Theoretical studies of clonal selection: minimal antibody repertoire size and reliability of self-non-self discrimination. J Theor Biol. 1979 Dec 21;81(4):645–670. doi: 10.1016/0022-5193(79)90275-3. [DOI] [PubMed] [Google Scholar]
  17. Sheriff S., Silverton E. W., Padlan E. A., Cohen G. H., Smith-Gill S. J., Finzel B. C., Davies D. R. Three-dimensional structure of an antibody-antigen complex. Proc Natl Acad Sci U S A. 1987 Nov;84(22):8075–8079. doi: 10.1073/pnas.84.22.8075. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Silver M. L., Parker K. C., Wiley D. C. Reconstitution by MHC-restricted peptides of HLA-A2 heavy chain with beta 2-microglobulin, in vitro. Nature. 1991 Apr 18;350(6319):619–622. doi: 10.1038/350619a0. [DOI] [PubMed] [Google Scholar]
  19. de Boer R. J., Perelson A. S. Size and connectivity as emergent properties of a developing immune network. J Theor Biol. 1991 Apr 7;149(3):381–424. doi: 10.1016/s0022-5193(05)80313-3. [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