A mathematical framework for analyzing T cell receptor scanning of peptides.
T cells continuously search for antigenic peptides presented on major histocompatibility complexes expressed on nearly all nucleated cells. Because only a few antigenic peptides are presented in a sea of thousands of self-peptides, the T cells have a critical task in discriminating between self- and nonself-peptides. This search process for antigens must be performed with sufficient speed in order to induce a fast response against invading pathogens. This study presents a mathematical framework for analyzing the scanning process of peptides. The framework includes analytic expressions for calculating the sampling rate as well as continuous-systems- and stochastic-agent-based models. The results show that the scanning of self-peptides is a very fast process due to fast off-rates. The simulations also predict the existence of an optimal sampling rate for a certain range of on-rates based on the recently proposed confinement time model. Calculations reveal that most of the self-peptides located within a microdomain are scanned within just a few seconds, and that the T cell receptors have kinetics for self-peptides, facilitating fast scanning. The derived mathematical expressions within this study provide conceptual calculations for further investigations of how the T cell discriminates between self- and nonself-peptides.
Infofusion, Systems Biology Research Centre, School of Life Sciences, University of Skövde, Skövde, Sweden. andreas.jansson@his.se
Andreas
A
Jansson
D000941:Antigens / Q000378:metabolism; D001324:Autoantigens / Q000378:metabolism; D055592:Biophysical Phenomena; D006680:HLA Antigens / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008213:Lymphocyte Activation; D018448:Models, Immunological; D010455:Peptides / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D013269:Stochastic Processes; D013601:T-Lymphocytes / Q000276:immunology*
D000941:Antigens; D001324:Autoantigens; D006680:HLA Antigens; D010455:Peptides; D011948:Receptors, Antigen, T-Cell