IMMUNOREGULATORY ACTIVITY OF THE T-CELL RECEPTOR ALPHA-CHAIN DEMONSTRATED BY RETROVIRAL GENE-TRANSFER

We have previously described an antigen-specific I-A(d)-restricted T-cell hybridoma, A1.1, that constitutively releases an antigen-specific immunoregulatory activity into supernatants. Using retrovirally mediated gene transfer, we have found that transfer of the T-cell receptor alpha-chain (TCR-alpha) gene from A1.1 to a number of other T-cell hybridomas effectively transferred the ability to produce the activity. Gene transfer of the TCR-beta chain (TCR-beta), however, did not transfer this ability. The regulatory activity from cells expressing the A1.1 TCR-alpha bound to and was eluted from an anti-TCR-alpha monoclonal antibody and displayed fine antigenic specificity identical to that of supernatants from A1.1. The possibility that this activity represents a secreted form of the TCR-alpha (as opposed to shed cell-surface TCR) was examined in BW1100 cells, lacking TCR-alpha and TCR-beta, which produced the antigen-specific activity after gene transfer of the A1.1 TCR-alpha gene. The expression of the immunoregulatory activity in supernatants correlated with a direct antigen-binding activity as detected by ELISA, thus raising the possibility that antigen binding is relevant to the mechanism of action of the soluble TCR-alpha. We discuss these observations and our earlier studies suggesting an immunoregulatory role for soluble TCR-alpha.