T cell repertoire selection in T cell receptor transgenic mice.

T cell receptor (TCR) gene segments begin to rearrange in CD4-8-thymic lymphoblasts. In severe combined immune deficiency (scid) mice the development of T cells is arrested at this early stage as the scid thymus does not contain any CD4+ or CD8+ lymphocytes. This block in T cell development can be overcome by introducing productively rearranged TCR genes into the scid strain which results in the formation of CD4+8+ lymphocytes. While this early differentiation step requires TCR's of any specificity, later developmental stages depend on the specificity of the TCR: in scid mice, a transgenic TCR restricted by Db class I major histocompatibility complex (MHC) antigens allows the formation of CD4-8+ but not CD4+8- lymphocytes in Db positive but not Db negative animals. Thus, a TCR-MHC interaction in the absence of nominal antigen is required for the generation of mature T cells, and this interaction determines the CD4/CD8 phenotype. If both nominal antigen and presenting MHC antigen are present developing T cells are deleted at an immature CD4+8+ stage preventing the formation of more mature and functional autoaggressive T cell progeny. These experiments indicate that the immune system first learns about self by positive and negative selection of self recognizing lymphocytes from a continuously turning over pool of lymphocytes without requirement for idiotypic network interactions.