1452 Resting T Cell Activation

The structure of the putative T cell antigen receptor has been defined using monoclonal antibodies (mAb) 1 prepared against various monoclonal T cell populations in several laboratories (1-3), including our own (4, 5). These reagents have defined an 80-90 kilodalton (kD) disulfide-linked heterodimer usually composed of a 49-53 kD alpha chain of acidic pI and a 41-43 kD beta chain of more basic pI. These heterodimeric molecules fulfill certain anticipated characteristics for the T cell antigen receptor, i.e., the presence of idiotypy (1-6), homology of the gene sequences to immunoglobulin (7-10), and the capacity to block the function of antigen-specific T cell lines or hybridomas when complexed with mAb that detect private idiotypes on the molecule (2, 3, 6). An additional functional characteristic expected of the T cell receptor is the ability to specifically mediate stimulation of resting T cells after interaction with antigen. This issue has been approached previously by using mAb that bind to the variable region of the antigen receptor on activated cells, such as interleukin 2 (IL-2)dependent T cell lines, T-T hybridomas, or human T cell leukemias that express the Tac antigen. When present either as soluble or Sepharose-bound antibody, these mAb have been shown (2, 3, 5, 6) to specifically increase IL-2 production or DNA synthesis in these previously activated cells. However, since these antibodies bind to private idiotypic specificities, they have not been useful in demonstrating a comparable pattern of activation with normal resting T cells. Recently, heteroantisera (11, 12) and mAb (4, 13) have been described that detect common determinants on the T cell antigen receptor expressed on normal T cells. Although these reagents confirm the presence of this molecule on normal T cells, they have not been reported to stimulate the reactive cells. In a previous report (4), we described an antibody reacting with the T cell antigen receptor on a subpopulation of normal circulating human T cells. This mAb, $511, was produced using a human T cell leukemia as the immunogen and was shown to immunoprecipitate an 80 kD, disulfide-linked heterodimer