Frontiers in Immunology (Oct 2013)
Co-receptor CD8-mediated modulation of T-cell receptor functional sensitivityand epitope recognition degeneracy
Abstract
The interaction between T-cell receptors (TCRs) and peptideepitopes is highly degenerate: a TCR iscapable of interacting productively with a wide range of differentpeptide ligands, involving not only crossreactivity proper(similar epitopes elicit strong responses), but alsopolyspecificity (ligands with distinct physicochemical properties arecapable of interacting with the TCR). Degeneracydoes not gainsay the fact that TCR recognition is fundamentallyspecific: for the vast majority of ligands, the functionalsensitivity of a given TCR is virtually null whereas this TCR has an appreciablefunctional sensitivity only for a minute fraction of all possible ligands.Degeneracy can be described mathematically as the probability that the functionalsensitivity, of a given TCR to a randomly selected ligand, exceeds aset value. Variation of this value generates a statisticaldistribution that characterizes TCR degeneracy. This distributioncan be modelled on the basis of a Gaussian distribution for theTCR/ligand dissociation energy. The kineticsof the TCR and the MHCI molecule can be used to transform thisunderlying Gaussian distribution into the observed distribution of functionalsensitivity values. In the present paper, the model is extended byaccounting explicitly for the kinetics of the interaction betweenthe co-receptor and the MHCI molecule. We show that T-cells canmodulate the level of degeneracy byvarying the density of co-receptors on the cell surface. This couldallow for an analogue of avidity maturation during incipientT-cell responses.
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