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

Jerome Percus, Ora E. Percus, Alan S. Perelson

Research output: Contribution to journalArticle

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 tune 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. Evolutionary, 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.

Original languageEnglish (US)
Pages (from-to)1691-1695
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume90
Issue number5
StatePublished - Mar 1 1993

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T-Cell Antigen Receptor
Immune System
Antibodies
Autoantigens
Major Histocompatibility Complex
Immunoglobulins
Epitopes
Observation
Ligands
Antigens
Peptides

Keywords

  • Epitopes
  • Self-nonself discrimination

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

Predicting the size of the T-cell receptor and antibody combining region from consideration of efficient self-nonself discrimination. / Percus, Jerome; Percus, Ora E.; Perelson, Alan S.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 90, No. 5, 01.03.1993, p. 1691-1695.

Research output: Contribution to journalArticle

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