Figure 8.

A model of thymocyte differentiation in which the relative balance of signals delivered by TCR engagement and lck activation is responsible for directing commitment to the CD4 and CD8 lineages. Engagement of TCR with particular MHC/peptide ligands can give partial antagonist–like signals with relatively little lck activation that is appropriate for commitment to the CD8 lineage in the thymus. Increasing the concentration of such peptides may increase the TCR engagement and promote an lck signal, which results in deletion but not differentiation to the CD4 lineage. In contrast, MHC/peptide interactions that result in a relatively high lck to TCR signal ratio specify commitment to the CD4 lineage. Thus overexpression of coreceptors with class I TCR transgenes could disproportionately increase the lck signal relative to the TCR signal and result in commitment to the CD4 lineage. On the other hand, class II–restricted TCR transgenes on a CD4° background would not receive a CD4-associated lck signal upon MHC/peptide engagement, leading to a predominant TCR to lck signal, which would favor commitment to the CD8 lineage.