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 Vbeta8.2+ and each of the required CD4 and CD8 regulatory T-cell populations are specific for different conserved regions of the Vbeta8.2 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.