Differential presentation of an altered peptide within fetal central and peripheral organs supports an avidity model for thymic T cell development and implies a peripheral readjustment for activation

Altered self peptides may drive T cell development by providing avidity of interactions low enough to potentiate positive selection but not powerful e nough to trigger programmed cell death. Since the peptide repertoire in bot h central and peripheral organs is nearly the same, interactions of these p eptides with T cells in the thymus would have to be different from those ta king place in the periphery; otherwise, T cell development and maturation w ould result in either autoimmunity or T cell deficiency. Herein, a self and an altered self peptide were delivered to fetuses, and their presentation as well as the consequence of such presentation on T cell development were assessed. The results indicate that the self peptide was presented in both central and peripheral fetal organs and that such presentation abolished T cell responses to both peptides during adult life, However, the altered pep tide, although presented in vivo as well as in vitro by splenic cells, was unable to stimulate a specific T cell clone when the presenting cells were of thymic origin and allowed offspring to be responsive to both peptides, T hese findings indicate that central and peripheral organs accommodate selec tion and peripheral survival of T cells by promoting differential altered p eptide presentation.