Somatic Cell Genetics of Cytolytic T Lymphocytes

Abstract

I would like to make some general comments about the use of cell genetics in the analysis of cytolytic mechanisms. To start you might well ask why somatic cell genetics, what is the importance of somatic cell genetics? I would answer that if you want to prove to me that you have identified a molecule on a CTL which is important for, say, its cytolytic activity, you can do it in one of two ways: You can either put this molecule into a vesicle or liposome of completely defined composition and show that this liposome has cytolytic activity; and I think it is quite clear that we are far from being able to do that type of experiment. Or you can use a cytolytic T-cell line which expresses the molecule and derive from this cell line variants which lack this molecule and show that they are no longer able to kill target cells. If such variants are the result of gene mutations then their further analysis should lead to testable hypotheses concerning the genetic control and the mechanism of cytolysis, as well as the differentiation of CTL. Now, let me outline briefly what the prerequisites for a somatic cell genetic analysis of a differentiated function are. The first one is that you have cell lines, i.e. cloned established cell populations, which stably express the function that you want to study.