DIFFERENTIAL ACTIVATION OF T-CELLS BY ANTIBODY-MODULATED PROCESSING OF THE FLANKING SEQUENCES OF CLASS II-RESTRICTED PEPTIDES

Despite poor presentation of measles virus (MV) nucleoprotein (NP) by MHC class II of infected cells, NP-specific antibodies are one of the hallmarks of the early immune response against this virus, To study th e influence of antibodies on processing and presentation of up to thre e different T cell hybridomas, mAb recognizing distinctive linear NP e pitopes were developed, Two T cell hybridomas TNP408B and TNP408 react ed with the same core epitope of NP (amino acids 383-391), but differe d in their sensitivity to the flanking sequences of peptides containin g this epitope, TNP408B reacted with minimal concentrations of NP when this was complexed with mAb BNP146, NP alone or saturating concentrat ions of other mAb did not activate this T cell, Both T cells, TNP408 a nd TNP408B, were similar in their sensitivity to NP in the presence of saturating concentrations of BNP146 or of appropriate peptide (NP379) , TNP408 did not differ from another T cell hybridoma (TNP79) in its s ensitivity to different mAb, suggesting a specificity-dependent and a specificity-independent effect of mAb, Antibody-mediated activation wa s attributed to FcR-mediated uptake independent of the fine specificit y of the mAb, In the case of TNP408B, this effect was further enhanced by a specific effect of BNP146, While all NP-specific mAb were suffic ient to enhance presentation to TNP408 and TNP79 of their respective p eptides derived from processed NP, BNP146 was necessary to generate th e peptides with the proper flanking sequences required by TNP408B, Sin ce the binding site of BNP146 coincides with the T cell epitope of TNP 408B (and TNP408) it is suggested that binding of this mAb modulates p rocessing of the flanking sequences of the peptides corresponding to t his epitope, This study shows that antibodies can influence the T cell response to an antigenic protein quantitatively and qualitatively by taking advantage of the sensitivity of T cells to flanking sequences o f class II-restricted peptides.