THYMIC SELECTION OF IMMUNOGLOBULIN IDIOTYPE SPECIFIC T-CELLS

The thymus is the major site for differentiation and maturation of developing T-cells. The diversity in the T-cell repertoire is generated during ontogeny by rearrangements of T-cell receptor gene segments that encode clonally distributed receptors. Most of the newly produced thymocytes that bear alpha beta TCR die in the thymus as a consequence of at least two selective processes. Those that can react to self MHC antigens survive (positive selection), but only if the binding affinity for the same or other self MHC (probably complexed with self peptides) molecules is not too high (negative selection). As a result, each T-cell that has acquired functional competence in the thymus should have a certain degree of self-MHC specificity. Our comprehension of thymic development has been aided by the study of transgenic mice that bear functionally rearranged TCR or Ig lambda light chain genes. To study positive selection we analyzed transgenic mice with alpha beta TCR genes isolated from a T-cell clone specific for an idiotypic peptide of lambda 2(315) (a mutant of the lambda 2 Ig chain) bound to the E(d) MHC class II molecule. The results suggest that positive selection of some thymocytes might be weak, reminiscent of a 'struggle for survival', since the selected population was small and had high levels of transgenic receptor and coreceptor (CD4) molecules. The thymic tolerance mechanism was also investigated using a combination of both TCR and lambda 2(315) transgenic mice. The clonal deletion of Id specific thymocytes was influenced by the production site as well as the concentration of the lambda 2(315) antigen. In conclusion, the interaction avidity of a single thymocyte, which is important for selective processes, might be affected by the expression levels of each interacting component: TCR, CD4 or CD8 and MHC molecule and self antigen.