title: Non-random pairing of CD46 isoforms with skewing towards BC2 and C2 in activated and memory/effector T cells.
abstract: CD46 is a glycoprotein with important functions in innate and adaptive immune responses. Functionally different isoforms are generated by alternative splicing at exons 7-9 (BC and C isoforms) and exon 13 (CYT-1 and CYT-2 isoforms) giving rise to BC1, BC2, C1 and C2. We developed a novel real-time PCR assay that allows quantitative comparisons between these isoforms. Their relative frequency in CD4+T cells from 100 donors revealed a distribution with high interpersonally variability. Importantly, the distribution between the isoforms was not random and although splicing favoured inclusion of exon 8 (BC isoforms), exclusion of exon 8 (C isoforms) was significantly linked to exclusion of exon 13 (CYT-2 isoforms). Despite inter-individual differences, CD4+and CD8+T cells, B cells, NK cells and monocytes expressed similar isoform profiles intra-individually. However, memory/effector CD4+T cells had a significantly higher frequency of CYT-2 when compared with naïve CD4+T cells. Likewise, in vitro activation of naïve and total CD4+T cells increased the expression of CYT-2. This indicates that although splicing factors determine a certain expression profile in an individual, the profile can be modulated by external stimuli. This suggests a mechanism by which alterations in CD46 isoforms may temporarily regulate the immune response.
authors.affiliation: Department of Biomedicine, Aarhus University, DK-8000 Aarhus C, Denmark.
authors.forename: Aida S
authors.initials: AS
authors.lastname: Hansen
authors.affiliation: Department of Biomedicine, Aarhus University, DK-8000 Aarhus C, Denmark.
authors.forename: Bettina B
authors.initials: BB
authors.lastname: Bundgaard
authors.affiliation: Department of Clinical Immunology, Aarhus University Hospital, DK-8200 Aarhus N, Denmark.
authors.forename: Bjarne K
authors.initials: BK
authors.lastname: Møller
authors.affiliation: Department of Biomedicine, Aarhus University, DK-8000 Aarhus C, Denmark.
authors.forename: Per
authors.initials: P
authors.lastname: Höllsberg
mesh_terms: D000328:Adult; D017398:Alternative Splicing; D000818:Animals; D016466:CHO Cells; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D008213:Lymphocyte Activation; D051916:Membrane Cofactor Protein / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
chemical_list: D051916:Membrane Cofactor Protein; D020033:Protein Isoforms