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Leukocyte common antigens (LCAs, also known as T200 and CD 45) are integral membrane proteins expressed exclusively on hematopoietic cells. These molecules exhibit varying molecular masses and epitopes when expressed in different cell types. To determine the genetic bases for the generation of this diversity, three classes of human LCA cDNA clones that are different near their 5' ends have been isolated. These differences arose as a result of differential usage of three exons as determined from an analysis of a genomic DNA clone. Furthermore, Northern blot analysis with LCA exon-specific probes demonstrates the existence of at least two more LCA mRNA forms that are generated by differential splicing. A comparison of the human and mouse LCA protein sequences revealed a marked difference only in the extracellular domain.