Analysis of T Cell Receptor Beta Chains in Rat Thymus, and Rat C Alpha and C Beta Sequences

In development, T cells first express their alpha beta antigen receptors in the thymus, where they may undergo selection processes leading to major histocompatibility complex (MHC) restriction and tolerance. A high proportion of thymocytes are thought to fail this selection in some way and to be destined for intrathymic death. These cells are categorized as the "cortical type" since they constitute most of the cortical cells; they express both CD4 and CD8 antigens but only very low levels of MHC class I antigens. One suggested cause of thymocyte death is a failure to produce a functional alpha beta T cell receptor (Tcr) due to errors in the rearrangements of germline DNA, resulting in V regions being absent or incorrectly spliced to the other segments of the transcribed gene. We have sequenced from the C region through to the V region of 14 rat Tcr beta chain clones isolated from thymocyte cDNA libraries. Of the 14, 13 have complete and correct rearrangements, whereas one was expressed from an unrearranged gene. Most of these clones are likely to be derived from the cortical population, for Northern blot analysis showed that these cells and total thymocytes expressed similar amounts of beta chain mRNA. Furthermore, the RNA from cortical-type cells contained a very similar ratio of full-length to truncated beta chain mRNA as did activated thymocytes and mature T lymphocytes. The data imply that defective beta chain gene rearrangement is not a major cause of failure in the selection of thymocytes. The sequences of the rat Tcr alpha and beta chain constant regions are also reported.