The goal of this research is to isolate and characterize genes whose products define important immunological functions. Using a messenger RNA subtraction procedure, we are able to derive cell type specific, 32p labeled cDNA probes which represent very small fractions (2.5 % - .25 %) of overall gene expression. We intend to use such probes to isolate differentially regulated genes encoded by two important genetic regions of the immune system; the H-2 region of the mouse, with emphasis on the I and S regions, and B cell specific genes of the X chromosome. Using genomic clones covering over 1000kb adjacent to and including the H-2 locus, we will screen for and characterize B, T and liver cell specific genes and their products which may influence antigen presentation or T supressor functions (I region) or code for complement fixing proteins (S region). We have demonstrated this technique in the isolation of a previously undetected Ia-alpha chain gene. We will also use B cell specific probes and somatic cell hybrid lines to screen for X-linked genes. There appear to be a small number of such genes, (perhaps 10) and that since there are two known X-linked immunodeficiencies in the mouse and at least seven in humans which affect B lymphocyte cells, the prospect of matching one or more genes with particular genetic lesions seems favorable. Such a correlation would be a valuable clue as to the function of the particular gene and be important to our understanding of the corresponding disease state. In addition, such gene/mutation combinations may provide attractive model systems for gene therapy.
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