Figure 4.

Data derived from in vivo positive and negative selection as interpreted by the experiments shown in Figs. 2 and 3. Shown are T cell receptors binding to agonist peptides and to antagonist peptides. The agonist peptides used to bind to the TCR induce dimer formation, but only in the presence of self-peptides, leading to activation followed by deletion in the thymus (panel 1). Y-Ae analogue peptide, which can positively select thymocytes, causes binding but not deletion. These self-peptides do not induce dimer formation, although they bind to the TCR. As a result of binding, these peptides induce positive selection in the thymus and sustain T cells in the periphery (27). Panel 3 shows what happens when the TCR does not bind to any peptide, leading to death by neglect. Our favored interpretation of the paradoxical positive selection seen with covalently linked agonist peptide in the absence of invariant chain and the endogenous I-A (panel 4) shows that all of the TCRs on a thymocyte adopt the same conformation and thus cannot aggregate, leading to positive selection. See text for further details.