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Co-receptor CD8-mediated modulation of T-cell receptor functional sensitivity and epitope recognition degeneracy
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Szomolay, Barbara, Williams, Tamsin, Wooldridge, Linda and Berg, Hugo van den (2013) Co-receptor CD8-mediated modulation of T-cell receptor functional sensitivity and epitope recognition degeneracy. Frontiers in Immunology, Volume 4 . p. 329. doi:10.3389/fimmu.2013.00329 ISSN 1664-3224.
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Official URL: http://dx.doi.org/10.3389/fimmu.2013.00329
Abstract
The interaction between T-cell receptors (TCRs) and peptide epitopes is highly degenerate: a TCR is capable of interacting productively with a wide range of different peptide ligands, involving not only cross-reactivity proper (similar epitopes elicit strong responses), but also polyspecificity (ligands with distinct physicochemical properties are capable of interacting with the TCR). Degeneracy does not gainsay the fact that TCR recognition is fundamentally specific: for the vast majority of ligands, the functional sensitivity of a given TCR is virtually null whereas this TCR has an appreciable functional sensitivity only for a minute fraction of all possible ligands. Degeneracy can be described mathematically as the probability that the functional sensitivity, of a given TCR to a randomly selected ligand, exceeds a set value. Variation of this value generates a statistical distribution that characterizes TCR degeneracy. This distribution can be modeled on the basis of a Gaussian distribution for the TCR/ligand dissociation energy. The kinetics of the TCR and the MHCI molecule can be used to transform this underlying Gaussian distribution into the observed distribution of functional sensitivity values. In the present paper, the model is extended by accounting explicitly for the kinetics of the interaction between the co-receptor and the MHCI molecule. We show that T-cells can modulate the level of degeneracy by varying the density of co-receptors on the cell surface. This could allow for an analog of avidity maturation during incipient T-cell responses.
Item Type: | Journal Article | ||||
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Subjects: | Q Science > QR Microbiology Q Science > QR Microbiology > QR180 Immunology |
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Mathematics | ||||
Library of Congress Subject Headings (LCSH): | T cells -- Receptors, Antigenic determinants, Peptides -- Immunology | ||||
Journal or Publication Title: | Frontiers in Immunology | ||||
Publisher: | Frontiers Research Foundation | ||||
ISSN: | 1664-3224 | ||||
Official Date: | October 2013 | ||||
Dates: |
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Volume: | Volume 4 | ||||
Page Range: | p. 329 | ||||
DOI: | 10.3389/fimmu.2013.00329 | ||||
Status: | Peer Reviewed | ||||
Publication Status: | Published | ||||
Access rights to Published version: | Open Access (Creative Commons) | ||||
Date of first compliant deposit: | 23 June 2016 | ||||
Date of first compliant Open Access: | 23 June 2016 | ||||
Funder: | Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC), Wellcome Trust (London, England) | ||||
Grant number: | WT079848MA, WT096454AIA, WT099067AIA (WT) |
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