Abstract
The binding of antibody or T-cell receptors to antigen occurs by a generalized lock and key fit of portions of the two structures. The question that we address here is: how large should the complementary regions on the two structures be? In order to estimate the size of an optimal receptor combining region, we assume that the mammalian immune system over evolutionary time has been presented with a large random set of foreign antigens that occur on common pathogens, which it must recognize, and a smaller random set of self-antigens which a mature organism must not recognize. Evolution is imagined to have coevolved the receptors in a fashion such as to maximize the probability that this task is performed. The probability of a random receptor-antigen match is estimated from this condition. For protein antigens, the genesis of the probability is traced to the complementarity of sufficiently long sequences of amino acids on the two molecules involved, and computed accordingly. The result is quite insensitive to the population sizes inserted, and results in an estimated 13-site binding region, in agreement with experimental information.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Amit, A. G., Mariuzza, R. A., Phillips, S. E. V., and Poljak, R. J. (1986) Three dimensional structure of an antigen-antibody complex at 2.8 A resolution, Science 233, 747–753.
Berzofsky, J. A,, and Berkower, I. J. (1989) Immunogenicity and antigen structure. In Fundamental Immunology, Paul, W. E., ed., Raven Press, NY, p. 185.
Cancro, M. P., Gerhard, W. and Klinman, N. R. (1978). The diversity of the influenzaspecific primary B-cell repertoire in Balb/c mice, J. Exp. Med. 147, 776–786.
Chalufour, A., Bougueleret, L., Claverie, J.-M., and Kourilsky, P. (1987) Rare sequence motifs are common constituents of hypervariable antibody regions, Ann. Inst. Pasteur/Immunol. 138, 671–685.
Claverie, J.-M., Kourilsky, P., Langlade-Demoyen, P., Chalufour-Prochnicka, Dadaglio, G., Tekaia, F., and Bougueleret, L. (1988) T-immunogenic peptides are constituted of rare sequence patterns. Use in identification of T epitopes in the human immunodeficiency virus gag protein. Eur. J. Immunol. 18, 1547–1553.
Coutinho, A. (1980) The self-nonself discrimination and the nature and acquisition of the antibody repertoire, Ann. Immunol. Inst. Past. 131D, 235.
Inman, J. K. (1978). The antibody combining region: speculations on the hypothesis of general multispecificity. In Theoretical Immunology, Bell. G. I., Perelson, A. S., and Pimbley, G. H. Jr., eds., Marcel Dekker, NY, pp. 243–278.
Kabat, E. A. (1976) Structural Concepts in Immunology and Immunochemistry, 2nd ed., Holt, Rinehart and Winston, NY.
Karlin, S., Ost, F., and Blaisdell, B. E. (1989). Patterns in DNA and amino acid sequences and their statistical significance. In Mathematical Methods for DNA Sequences, M. S. Waterman, ed., CRC Press, Boca Raton, FL.
Klein, J. (1990). Immunology, Blackwell Scientific, Boston.
Perelson, A. S. and Oster, G. F. (1979) Theoretical studies of clonal selection: Minimal antibody repertoire size and reliability of self-nonself discrimination, J. Theoret. Bio. 81, 645–670.
Sheriff, S., Silverton, E. W., Padlan, E. A., Cohen, G. H., Smith-Gill, S. J., Finzel, B. C., and Davies, D. R. (1987) Three-dimensional structure of an antibody-antigen complex, Proc. Natl. Acad. Sci. USA 84, 8075–8079.
Uspensky, J. V. (1937). Introduction to Mathematical Probability, McGraw-Hill, NY, pp. 77–84.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1992 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
Percus, J.K., Percus, O.E., Perelson, A.S. (1992). Probability of Self-Nonself Discrimination. In: Perelson, A.S., Weisbuch, G. (eds) Theoretical and Experimental Insights into Immunology. NATO ASI Series, vol 66. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-76977-1_5
Download citation
DOI: https://doi.org/10.1007/978-3-642-76977-1_5
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-76979-5
Online ISBN: 978-3-642-76977-1
eBook Packages: Springer Book Archive