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Thymocyte selection

In contrast to the TcR repertoire of immature thymocytes which is vast and largely results from V-(D)-J recombination, the TcR repertoire expressed by mature T cells is largely devoid of autoreactivity and is restricted to recognizing foreign peptides in the context of self-MHC molecules [1].

In the thymus, immature CD4+ CD8+ (DP) thymocytes undergo three different fates depending from the T cell receptor specificity and avidity to the thymic ligands, although the differences can be relatively small.

There is a kinetic threshold between negative and positive selection based on the longevity of the T cell receptor ligand complex (dwell time of the receptor with its ligand) [2]. High affinity TcR/ligand interactions would result in a dwell time that allows complete progression of the signalling pathway and the formation of late activation complexes, resulting in negative selection. In contrast, low-affinity interactions with short dwell times would result in premature attenuation of the signalling cascade and positive selection [3].

[1] Sebzda, E. et al. Annu. Rev. Immunol. 17, 829-874 (1999).
[2] Williams, C. B. et al. J. Exp. Med. 189, 1531-1544 (1999).
[3] Love, P. E. and Shores, E. W. Immunity 12, 591-597 (2000).