Epitopic analysis of HLA DR molecule expression on alloreactive T-cell clones

The expression of HLA-DR epitopes, recognized by a set of anti-DR MoAbs clustered into four groups according to immunochemical studies, was analyzed at the surface of in vivo-sensitized alloreactive T-cell clones derived from a rejected kidney allograft and on the autologous B lymphoblastoid cell line (BLCL). Although no clear-cut differences were noted between T cells themselves and T cells vs BLCL in the relative expression of most of the DR epitopes studied (D1.12, BT2/9, VI.15C, 135, 206, 141, BM50), relative and absolute expression of one DR epitope (BMMag8) was strikingly higher on autologous BLCL than on T-cell clones. Moreover, the absolute expression of DR epitopes was heterogeneous among T cells. Such differences could not be explained either by T-cell activation level (assessed by IL2 receptor or transferrin receptor expressions) or by differences in time kinetics expression. In other tests, anti-DR MoAbs were assayed for their ability to block cytotoxic activity of several T-cell clones directed against DR allospecificities. Each T-cell clone showed distinct inhibition patterns. By such analysis, it was possible to define several groups of epitopes not always identical to those defined by immunochemical studies. Finally, analysis of the ability of MoAb to specifically block cytotoxicity mediated by 2 anti-DRw8 T-cell clones at the target level allowed precise epitopic study of polymorphic DRw8 determinants recognized by these cells, in this case borne by a single DR alpha/beta heterodimer.