The Role of the Fc Receptor in T‐Cell Activation

The repertoire of T-cell specificities is determined during the maturation of Tcells in the thymus. The available evidence suggested that T cells are selected into an individual's T-cell compartment on the basis of their ability to recognize auto-major histocompatibility complex (MHC) antigens [12]. T-helper (TH) cells recognize class II antigens, and cytotoxic cells recognize class I antigens [9,17]. The specificity of T cells for a given MHC antigen epitope is controlled by its clonotypic T-cell receptor (TCR) [8]. After their recruitment T cells exit from the thymus into the periphery, where they recognize autoMHC antigen in conjunction with foreign antigen but no longer do so spontaneously. The question arises as to what causes T cells to lose their ability to interact effectively with auto-MHC antigen. There are basically two possibilities; the T-cell receptor either diminishes its affinity for MHC antigen, or the organism installs down-regulatory mechanisms to reduce the consequences of auto-Ia recognition. There is no evidence to support the former assumption, although this possibility has been actively investigated. We believe that the second possibility deserves increased attention, and we present here the idea that the mixed lymphocyte stimulation (MLS) locus encodes a molecule which conveys a down-regulatory signal to TH cells when these cells interact with completely syngeneic antigenpresenting cells (APC). Whereas the normal function of the MLS signal is to counteract autoreactivity, our model also provides an explanation for the MLS effect. When T cells are mixed with accessory cells from MHC-identical individuals which differ at the MLS locus, this inhibitory signal can occasionally become inoperative, or less effective, and T-cell activation occurs on the basis of unobstructed autostimulation.