Transgenic T cell receptor interactions in the lymphoproliferative and autoimmune syndromes of lpr and gld mutant mice.

To investigate the role of T cell receptor (TcR) expression and interactions in development of lymphoproliferation and autoimmunity in lpr and gld mutant mice, and to determine whether these autoimmune mutations affect T cell selection and repertoire formation, we generated mice homozygous for either the gld or the lpr mutation and containing TcR alpha/beta transgenes (Von Boehmer, H., Annu. Rev. Immunol. 1990. 8: 531) specific for the male (H-Y) antigen in the context of H-2Db. Four main results emerged from analysis of these mice. First, expression of transgenic TcR had no effect on disease incidence and progression. Second, the accumulating T cells reflected normal processes of positive and negative selection. Third, cells expressing the transgenic TcR participated equally in lymphoproliferation regardless of whether their antigenic peptide and/or presenting major histocompatibility complex molecules were present or not. Fourth, expression of the TcR transgenes markedly altered the phenotype of the major accumulating lymphocyte subset. Thus, in these models of lymphoproliferation and autoimmunity. T cell repertoire formation proceeds normally, specific T cell recognition of antigen has no effect on the participation of individual clones, and the phenotype of the cells accumulating is sensitive to either the timing or the amount of TcR expression. These results are discussed in the context of the primary cause vs. secondary manifestations of autoimmunity in these models.