An approach to molecular analysis of T-cell clones by two-dimensional gel electrophoresis: is there interclonal and intraclonal heterogeneity?

To understand the regulation of immunity one must understand the processes and the consequences of the activation of the lymphoid cell, its clonal proliferation, and the ultimate differentiation of the progeny into the effector elements that constitute the immune system. By use of polyclonal mitogens, individual T-cell precursors can be activated for study of their clonal growth and generation of T effector cells. We used two-dimensional gel electrophoresis to study the gene products expressed by such T-cell clones. On comparing the radiofluorograms of such gels for a large set of T-cell clones we find that many gene products are expressed in common, as expected, but that another large set of products varies from one clone to the other and might be designated as markers of T-cell subsets or stages of differentiation. By subdividing the growing clone and analyzing the family of daughter clones, we find considerable variation in gene expression during clonal expansion.