RECOMBINANT SOLUBLE ALPHA-BETA-T-CELL RECEPTORS PROTECT T-CELLS FROM IMMUNE SUPPRESSION - REQUIREMENT FOR AGGREGATED MULTIMERIC, DISULFIDE-LINKED ALPHA-BETA HETERODIMERS

Recombinant soluble T cell receptors (sTCR) protected contact sensitiv ity (CS) effector T cells from down-regulation or immunosuppression, C S-protecting sTCR were released enzymatically from the surface of thym oma cells transfected with cDNAs encoding TCR-alpha and -beta extracel lular domains that were expressed with a phosphatidylinositol linkage, sTCR affinity purified on anti-TCR-alpha and anti-TCR-beta mAb column s had identical CS-protective activity, as did sTCR from a CD4(+) Th2 clone or from a CD8(+) cytotoxic clone, Reduced sTCR alpha- and beta-c hains had no CS-protective activity, but this was restored when the TC R chains were rejoined into disulfide-linked alpha beta heterodimers, sTCR CS protection was Ag nonspecific, MHC unrestricted, and not influ enced by the relevant synthetic peptide specific for the TCR complexed with appropriate MHC. CS protection may have resided in the sTCR cons tant region, When heated at 62 degrees C for 30 min, sTCR formed a CS- protecting aggregate, with a molecular mass of 481 +/- 37 kDa, corresp onding to an alpha beta TCR pentamer, HPLC gel Filtration essentially confirmed the molecular mass at 516 kDa for the multimer, while the mo nomer, which was an ap TCR heterodimer, had an expected molecular mass of similar to 104 kDa and no bioactivity, In summary, the pentameric sTCR may hind to and activate lymphoid cells, perhaps via constant dom ains, resulting in protection of CS effector T cells from down-regulat ion, The ability of sTCR to protect CS effector T cells from down-regu lation/suppression, ii generalized, could overcome immunosuppression a ccompanying infectious diseases, particularly AIDS, or in tumors.