B. Lucas et al., Divergent changes in the sensitivity of maturing T cells to structurally related ligands underlies formation of a useful T cell repertoire, IMMUNITY, 10(3), 1999, pp. 367-376
CD4(+)CD8(+) thymocyte differentiation requires TCR signaling induced by se
lf-peptide/MHC ligands. Nevertheless, the resulting mature T cells are not
activated by these self-complexes, whereas foreign ligands can be potent st
imuli. Here, we show that the signaling properties of TCR change during thy
mocyte maturation, differentially affecting responses to related peptide/MH
C molecule complexes and contributing to this discrimination. Weak agonists
for CD4(+)CD8(+) thymocytes lose potency during development, accompanied b
y a change in TCR-associated phosphorylation from an agonist to a partial a
gonist/antagonist pattern. in contrast, sensitivity to strong agonists is m
aintained, along with full signaling. This yields a mature T cell pool high
ly responsive to foreign antigen while possessing a wide margin of safety a
gainst activation by self-ligands.