An integrative model of regulation centered on recognition of TCR peptide/MHC complexes

We have described a T-cell receptor (TCR)-centered model of immune regulation, in which MHC/TCR peptide complexes provide for the activation of regulatory T cells and likewise act as their target structures. In this model, the disease-causing effectors are TCR V beta8.2(+) and each of the required CD4 and CD8 regulatory T-cell populations are specific for different conserved regions of the V beta8,2 chain, in the appropriate MHC context. We have characterized the dominance, the dynamics as well as the TCR usage of both effector and regulatory T cells. We have begun to characterize the essential elements of the regulatory program, including the mechanism of interaction among effector and regulatory T-cell populations. Principles learned in this model have important implications for immune regulation in general.