Non-random pairing of CD46 isoforms with skewing towards BC2 and C2 in activated and memory/effector T cells

• Published in: Scientific reports 2016-10, Vol.6 (1), p.35406-35406, Article 35406
• Main Authors: Hansen, Aida S., Bundgaard, Bettina B., Møller, Bjarne K., Höllsberg, Per
• Format: Article
• Language: English
• Subjects: 13/109; 13/21; 38/77; 38/90; 631/250/1619/554/1898; 631/250/2502/2170; Adaptive immunity; Adult; Alternative Splicing; Animals; CD4 antigen; Cells, Cultured; CHO Cells; Cricetinae; Cricetulus; Genes; Humanities and Social Sciences; Humans; Immune response; Immunology; Lymphocyte Activation; Lymphocytes; Lymphocytes T; Membrane Cofactor Protein - genetics; Membrane Cofactor Protein - metabolism; Middle Aged; multidisciplinary; Protein Isoforms - genetics; Protein Isoforms - metabolism; Science; Splicing factors; T-Lymphocytes - immunology; T-Lymphocytes - metabolism
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep35406

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.