HUMAN LANGERHANS CELLS EXPRESS A NOVEL FORM OF THE LEUKOCYTE COMMON ANTIGEN (CD45)

CD45 is a family of transmembrane glycoproteins that function as prote in tyrosine phosphatases. All isoforms exhibit common CD45 epitopes, w hereas the restricted CD45 epitopes (RA, RE, and RO) are each limited to one or more isoforms, In prior studies, we showed that human Langer hans cells in normal epidermis express a novel CD45 phenotype. They ex press common CD45 epitopes but are characteristically RA(-)RB(-)RO(-). This suggests that Langerhans cells can express a novel form of CD45. In order to clarify this issue further, mRNA extracted front enriched Langerhans cell preparations was reverse transcribed into cDNA, The 5 ' portion of CD45 cDNA was then amplified using polymerase chain react ion primers complementary to exon 2 and exons 9-10, which flank the CD 45 variable exon region (exons 4-6). Cloning and sequencing of the dom inant 441 by polymerase chain reaction product revealed the following exon configuration for the 5' translated region of Langerhans cells CD 45: exon 3/7/8/9/10, This is the same exon configuration associated wi th the 180 kd CD45 isoform expressed by memory T cells and monocytes/m acrophages; however, these cell types are RO+ whereas normal Langerhan s cells are RO-. The RO epitope is known to be an oligosaccharide with a terminal sialic acid moiety, Therefore, we determined the expressio n of a related epitope, OPD4, by Langerhans cells. This is another ter minal sialic acid moiety expressed by the 180 kd CD45 isoform of memor y T cells but not by monocytes/macrophages, Langerhans cells were OPD4 (-). Our data suggest that memory T cells, monocytes/macrophages, and Langerhans cells all express a common CD45 transcript lacking exons 4- 6; however, this transcript appears to undergo lineage-specific, post- translational glycosylation to create three distinct CD45 glycoprotein s: RO(+)OPD4(+), RO(+)OPD4(-), and RO(-)OPD4(-), which are expressed t ypically by memory T cells, monocytes/macrophages, and Langerhans cell s, respectively. Because these epitopes are located extracellularly, t hey are postulated to allow differential responses to extracellular st imuli by creating differential ligand specificity.