Human Langerhans cells express a novel form of the leukocyte common antigen (CD45).
CD45 is a family of transmembrane glycoproteins that function as protein tyrosine phosphatases. All isoforms exhibit common CD45 epitopes, whereas the restricted CD45 epitopes (RA, RB, and RO) are each limited to one or more isoforms. In prior studies, we showed that human Langerhans cells in normal epidermis express a novel CD45 phenotype. They express 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 from enriched Langerhans cell preparations was reverse transcribed into cDNA. The 5' portion of CD45 cDNA was then amplified using polymerase chain reaction primers complementary to exon 2 and exons 9-10, which flank the CD45 variable exon region (exons 4-6). Cloning and sequencing of the dominant 441 bp polymerase chain reaction product revealed the following exon configuration for the 5' translated region of Langerhans cells CD45: exon 3/7/8/9/10. This is the same exon configuration associated with the 180 kd CD45 isoform expressed by memory T cells and monocytes/macrophages; however, these cell types are RO+ whereas normal Langerhans cells are RO-. The RO epitope is known to be an oligosaccharide with a terminal sialic acid moiety. Therefore, we determined the expression of a related epitope, OPD4, by Langerhans cells. This is another terminal sialic acid moiety expressed by the 180 kd CD45 isoform of memory 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 glycoproteins: RO+ OPD4+, RO+ OPD4-, and RO- OPD4-, which are expressed typically by memory T cells, monocytes/macrophages, and Langerhans cells, respectively. Because these epitopes are located extracellularly, they are postulated to allow differential responses to extracellular stimuli by creating differential ligand specificity.
Department of Dermatology, and Skin Diseases Research Center, Case Western Reserve University, and the Veterans Affairs Medical Center, Cleveland, Ohio 44106, USA.
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Wood
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Szwejbka
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Schwandt
D000939:Epitopes / Q000096:biosynthesis; D005091:Exons / Q000235:genetics; D014644:Genetic Variation; D006801:Humans; D007801:Langerhans Cells / Q000276:immunology*; D017493:Leukocyte Common Antigens / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D014158:Transcription, Genetic / Q000502:physiology
D000939:Epitopes; D020033:Protein Isoforms; D017493:Leukocyte Common Antigens