Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
4497593 | Journal of Theoretical Biology | 2010 | 19 Pages |
Abstract
A potential mechanism that allows T cells to reliably discriminate pMHC ligands involves an interplay between kinetic proofreading, negative feedback and a destruction of this negative feedback. We analyse a detailed model of these mechanisms which involves the TCR, SHP1 and ERK. We discover that the behaviour of pSHP1 negative feedback is of primary importance, and particularly the influence of a kinetic proofreading base negative feedback state on pSHP1 dynamics. The CD8 co-receptor is shown to benefit from a kinetic proofreading locking mechanism and is able to overcome pSHP1 negative influences to sensitise a T cell.
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Authors
Nick D.L. Owens, Jon Timmis, Andrew Greensted, Andy Tyrrell,