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CD45 (leukocyte common) antigen is a hemopoietic cell-specific tyrosine phosphatase essential for antigen receptor-mediated signaling in lymphocytes. The molecule undergoes complex alternative splicing in the extracellular domain, and different patterns of CD45 splicing are associated with distinct functions. Lack of CD45 leads to severe combined immunodeficiency, and alterations of CD45 splicing, because of a polymorphism in exon 4, have been associated with altered immune function. Here we describe a polymorphism in exon 6 (A138G) of the gene encoding CD45 that interferes with alternative splicing. The polymorphism results in an amino acid substitution of Thr-47 to Ala in exon 6, a potential O- and N-linked glycosylation site. This exon 6 A138G variant is present at a frequency of 23.7% in the Japanese population but is absent in Caucasoids. Peripheral blood T cells from individuals carrying the A138G variant show a significant decrease in the proportion of cells expressing the A, B, and C CD45 isoforms and a high frequency of CD45R0+ cells. These phenotypic alterations in the A138G carriers may lead to changes in ligand binding, homodimerization of CD45, and altered immune responses, suggesting the involvement of natural selection in controlling the A138G carrier frequency.

Original publication

DOI

10.1073/pnas.0931490100

Type

Journal article

Journal

Proc Natl Acad Sci U S A

Publication Date

13/05/2003

Volume

100

Pages

5997 - 6002

Keywords

Adult, Aged, Aging, Asian Continental Ancestry Group, Base Sequence, Chromatography, High Pressure Liquid, DNA Primers, European Continental Ancestry Group, Exons, Female, Gene Expression Regulation, Enzymologic, Genital Neoplasms, Female, Geography, Heterozygote Detection, Homozygote, Humans, Intracellular Signaling Peptides and Proteins, Isoenzymes, Membrane Proteins, Middle Aged, Phosphoproteins, Polymorphism, Genetic, Reference Values