HIGH-FREQUENCY OF T-CELL LINES RESPONSIVE TO IMMUNODOMINANT EPITOPES OF THYROTROPIN RECEPTOR IN HEALTHY-SUBJECTS

In this study we analyzed the proliferative response to the extracellu lar domain of thyrotropin receptor (TSHR-ECD) of T-cell lines raised f rom healthy subjects. We found high frequencies of cell lines reactive to TSHR-ECD, ranging from 12% to 37%. The response of the cell lines to a set of overlapping peptides of TSHR-ECD showed that the most reco gnized epitopes by T lymphocytes are on the C-terminal portion. In par ticular, the regions of residues 360-396 and 258-277 are immunodominan t in T-lymphocyte reactivity. A group of cell lines specific for the p eptides of TSHR-ECD lost the response to the peptides during time in c ulture. However, these lines were still responsive to TSHR extracellul ar domain. The cloning of one of these lines showed three types of T-c ell clones: (1) CD4(+) clones (it = 4) highly responsive to the TSHR-E CD; (2) CD4(+) clones (n = 4) low responsive to TSHR-ECD; (3) CD8(+) c lones (n = 9) not responsive to TSHR-ECD. The first group of clones wa s stable during time in culture, while the second group was characteri zed by the loss of the specific response to TSHR-ECD after some weeks from the first analysis. The observation of a spontaneous anergy in th e second group of CD4(+) clones suggests that mechanisms of control of the lymphocyte response to TSHR-ECD could be activated in vitro.