Going Around Again

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Science  20 Oct 2000:
Vol. 290, Issue 5491, pp. 411
DOI: 10.1126/science.290.5491.411a

Thymocytes that fail to complete their program of development undergo cell death, either by neglect resulting from a failure to recognize antigen, or by deletion through encounter with an antigen for which they are highly self-reactive.

McGargill et al. suggest that some developing thymocytes may use a novel mechanism, akin to the receptor editing already known in B cell development, to avoid deletion. Transgenic mice were created that expressed a peptide antigen within the thymus. When presented with peptide, the reactive thymocytes were no longer susceptible to deletion. Instead, encounter with the antigen led to down-regulation of surface T cell receptor (TCR) and fresh rearrangement of the second TCR_ allele. This corresponded with extended expression of the recombinase-activating enzymes responsible for immune receptor gene rearrangement in B and T cells. In this way the door may be left open for small numbers of self-reactive T cells to try out once again for positive selection using a new receptor. — SJS

Nature Immunol.1, 336 (2000).

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