IMMUNOGENETICS OF LY SYSTEMS

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In achieving an understanding of what constitutes a program for cell surface composition, and ultimately its control, it is important to know the location of the genes that code the proteins of the several glycoproteins concerned. We report that the Lyt-1 locus of chromosome 19, and the Ly-5 locus of chromosome 1, are the sites of protein structural genes concerned in composing the surface phenotypes of particular lymphocyte classes. A central focus of interest in Ly-5, expressed by most or all hematopoietic cells, is the determination of different isoforms that characterize different hematopoietic cell lineages. It is shown that at least two of these isoforms differ in protein structure. A vital question now is whether and which isoforms are products of separate, linked genes whose produces share Ly-5 antigen, and which may be the products of post-transcriptional modification such as alternative splicing. Current work centers on the verification of an Ly-5 cDNA probe which we have cloned, and its use for that purpose. The nature and properties of variant leukemia lines that lack expression of class I genes are of interest in many contexts, among which is the relation of aberrant regulation of TL antigens in leukemia cells. It is shown that one such variant, which exhibits phenotypic loss of an entire H-2:Tla haplotype is a true genomic variant in which the genes of that haplotype have been lost, probably by somatic recombination accompanied by duplication of the remaining genomic haplotype. Allied variants will be studied with a view to establishing any necessary relation between retention of either Tla locus and malignancy. The cloning methods successfully applied to Ly-5 lend themselves to the cloning of other genes for differentiation antigen systems which this laboratory has defined, in particular Lyt-1, and also Tla, for which a sufficiently selective probe distinct from other class I genes is wanted, and studies to that effect are in hand. (CS)