Abstract
Previous analyses of T cell receptor beta chain (TcR beta) genomic DNA from subsets of human peripheral blood leukocytes suggested that the TcR beta methylation pattern might reflect distinct differentiation pathways. The studies presented here, using murine thymocyte subsets, have specifically addressed the question of whether methylation of TcR beta DNA is related to the cellular maturity and type of TcR beta mRNA expressed in the different subsets. We have observed that the DNA isolated from either CD4+ or CD8+ thymocytes, the more mature thymic subsets, is less methylated in the TcR beta region than DNA isolated from the CD4-CD8-, double-negative population containing the more immature thymocytes. In addition, this pattern of DNA methylation is directly related to the ratio of 1.3-kb to 1.0-kb TcR beta mRNA seen in these different cell types. Although a quantitative difference in the level of TcR beta mRNA was noted for the two mature subsets, no qualitative difference in the ratio of 1.3-kb to 1.0-kb mRNA was detected. Furthermore, these DNA methylation patterns appear to be lineage related, because the TcR beta region of genomic DNA isolated from mouse macrophages is heavily methylated.
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