The inhibition of different T cell lines specific for the same antigen with TCR antagonist peptides

To further understand and evaluate the phenomenon of TCR antagonism, we wished to determine whether analogs of an antigenic determinant could antagonize a specific polyclonal response. To this end, the ability of TCR antagonist peptides to inhibit a panel of five different DR4w4-restricted, influenza hemagglutinin 307-319-specific T cell lines was examined. An analysis of their V beta and J beta usage indicated that each of these five T cell lines expressed different TCR. A series of HA 307-319 single amino acid substituted analogs were used to determine the fine Ag specificities of the different lines. Ag analogs that demonstrated little or no stimulatory capacity were then examined for their ability to act as TCR antagonists by inhibiting the proliferative response of these five lines. Overall, 17 different peptide analogs capable of antagonizing at least one T cell line were identified. Although no single analog was capable of inhibiting all five T cell lines, two different analogs were identified that were capable of inhibiting four of five of the T cell specificities examined.