PEPTIDE ANTIGEN OR SUPERANTIGEN-INDUCED DOWN-REGULATION OF TCRS INVOLVES BOTH STIMULATED AND UNSTIMULATED RECEPTORS

T cell activation by peptide/MHC complexes, superantigens, or mAbs ind uces the down-regulation of cell surface TCRs. We addressed the questi on of whether TCR down-modulation affects only TCRs that had directly interacted with their ligand or whether down-modulation could also aff ect TCRs that had not interacted with their ligand. To this end, we ge nerated T cells coexpressing equal levels of two different TCRs by tra nsfecting the appropriate cDNAs into cells of the human T cell line, J urkat. Each set of TCRs can be distinguished by means of anti-vp mAbs and can be stimulated separately with peptide Ag, bacterial superantig ens, or mAbs. We found that activation of these cells with each of the se stimuli down-modulated not only directly stimulated TCR complexes b ut also unstimulated ones. Comodulation of stimulated and unstimulated receptors may reflect functional interactions between surface TCRs th at could take place during Ag or superantigen recognition by T cells w ithout the need for ligand cross-linking. Consistent with this idea, b oth stimulated and unstimulated receptors colocalized in patches on th e cell surface after activation.