P. Wong et al., Competition for specific intrathymic ligands limits positive selection in a TCR transgenic model of CD4(+) T cell development, J IMMUNOL, 164(12), 2000, pp. 6252-6259
Efficient positive selection of a broad repertoire of T cells is dependent
on the presentation of a diverse array of endogenous peptides on MHC molecu
les in the thymus. It is unclear, however, whether the development of indiv
idual TCR specificities is influenced by the abundance of their selecting l
igands, To examine this, we analyzed positive selection in a transgenic mou
se carrying a TCR specific for the human CLIP:I-A(b) class II complex. We f
ound that these mice exhibit significantly reduced CD4(+) T cell developmen
t compared with two other transgenic mice carrying TCRs selected on I-A(b).
Moreover, many of the selected cells in these mice express endogenous and
transgenic receptors as a consequence of dual TCR alpha expression. Dramati
c enhancement of the selection efficiency is observed, however, when fewer
transgenic cells populate the thymus in mixed bone marrow chimeras. These r
esults suggest that positive selection is limited by the availability of se
lecting peptides in the thymus, This becomes apparent when large numbers of
thymocytes compete for such peptides in TCR transgenic animals. Under such
conditions, thymocytes appear to undergo further TCR alpha gene rearrangem
ent to produce a receptor that may be selected more efficiently by other th
ymic self-peptides.