Antibodies to the C-terminal dipeptide of mouse mammary tumor virus [MMTV(SW)] superantigen effectively inhibit T-cell activation in vivo.

BALB/c mice were immunized against the 19 C-terminal amino acids of the mouse mammary tumour virus [MMTV(SW)] superantigen, either actively with the recombinant ORF19 protein or passively by subcutaneous implantation of 6E1.8 hybridoma cells. Protection against the MMTV(SW) superantigen-induced activation of specific T cells was obtained in both immunizations. Whereas the monoclonal antibody provided complete protection, similar antibody titres showed less effective protection in actively immunized mice. This was due to the presence of a histidine tag on the recombinant ORF19 protein preventing immune recognition of the C-terminal amino acids during immunization. Preincubation of the 6E1.8 monoclonal antibodies with modified ORF19 peptides at their C terminus established specific recognition of the last two amino acids of MMTV(SW) superantigen by this antibody, and showed that these amino acids are critical in the interaction between the MMTV(SW) superantigen and the Vbeta element of the T-cell receptor.