Differential usage of three exons generates at least five different mRNAs encoding human leukocyte common antigens.

Streuli, Michel; Hall, Laurie R.; Saga, Yumiko; Schlossman, S F; Saito, Haruo

doi:10.1084/jem.166.5.1548

Cited by 305 publications

(139 citation statements)

References 51 publications

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“…In the resting state, the majority of the cells express mainly the full-length CD6 form; upon productive T cell stimulation, there is a partial substitution of the full-length isoform by a substantial number of CD6 molecules per cell that no longer express the CD166 binding domain and thus are not restricted to the IS. This type of regulation of splicing is not unique, because it has long been known to control the expression of CD45 isoforms (51,52). The novel CD6 isoform reported in this study seems to have a more obvious function because it disables the interaction of the protein with its ligand.…”

Section: Discussionmentioning

confidence: 88%

Extracellular Isoforms of CD6 Generated by Alternative Splicing Regulate Targeting of CD6 to the Immunological Synapse

Castro

Oliveira

Nunes

et al. 2007

The Journal of Immunology

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The great majority of mammalian genes yield multiple transcripts arising from differential mRNA processing, but in very few instances have alternative forms been assigned distinct functional properties. We have cloned and characterized a new isoform of the accessory molecule CD6 that lacks the CD166 binding domain and is expressed in rat and human primary cells. The novel isoform, CD6Δd3, results from exon 5 skipping and consequently lacks the third scavenger receptor cysteine-rich (SRCR) domain of CD6. Differential expression of the SRCR domain 3 resulted in a remarkable functional difference: whereas full-length CD6 targeted to the immunological synapse, CD6Δd3 was unable to localize at the T cell:APC interface during Ag presentation. Analysis of expression of CD6 variants showed that, while being more frequent in coexpression with full-length CD6, the CD6Δd3 isoform constituted the sole species in a small percentage of T cells. In the rat thymus, CD6Δd3 is less represented in double-positive thymocytes but is detectable in nearly 50% of single-positive CD4 or CD8 thymocytes, suggesting that CD6 switching between full-length and Δd3 isoforms may be involved in thymic selection. Strikingly, CD6Δd3 is markedly up-regulated upon activation of T lymphocytes, partially substituting full-length CD6, as evaluated by RT-PCR analysis at the single-cell level, by immunoblotting, and by flow cytometry using Abs recognizing SRCR domains 1 and 3 of human CD6. This elegant mechanism controlling the expression of the CD166 binding domain may help regulate signaling delivered by CD6, through different types of extracellular engagement.

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Section: Discussionmentioning

confidence: 88%

Extracellular Isoforms of CD6 Generated by Alternative Splicing Regulate Targeting of CD6 to the Immunological Synapse

Castro

Oliveira

Nunes

et al. 2007

The Journal of Immunology

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“…This heterogeneity is due to the existence of celltype-specific alternative splicing from a common precursor mRNA that generates several CD45 mature mRNAs coding for proteins with distinct amino acid content of the N-terminal regions [5][6][7][8][9]. Variable carbohydrate composition also contributes to the heterogeneity found within the Correspondence address: F. S~mchez-Madrid, Servicio de Inmunologia, Hospital de la Princesa, c/Diego de Lern, no.62, 28006 Madrid, Spain Abbreviations: PBL, peripheral blood lymphocytes; PMA, phorbol myristate acetate; fMLP, N-formyl-methionyl-leucylphenylalanine CD45 molecular complex [10,11].…”

Section: Introductionmentioning

confidence: 99%

Biochemical and antigenic characterization of CD45 polypeptides expressed on plasma membrane and internal granules of human neutrophils

Pulido¹,

Lacal²,

Mollinedo³

et al. 1989

FEBS Letters

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The expression of CD45 polypeptides, a phosphotyrosine phosphatase complex specific of leukocytes, has been investigated in both resting and activated neutrophils by using anti-CD45 monoelonal antibodies (MAb) which specifically recognize different polypeptide components of the CIM5 molecular complex. Polypeptides of 180 and 130-150 kDa were equally precipitated by either a conventional CD45 MAb recognizing an antigenic determinant shared by the four CD45 glycoproteins (220, 205, 190 and 180 kDa) or by the anti-180 kDa UCHLI MAb. These polypeptides were overexpressed on neutrophil plasma membranes after degranulatory stimulation. Conversely, neither the anti-220 kDa CD45R nor anti-220/205/190 kDa MAb reacted with CD45 molecules from resting or activated neutrophils. Furthermore, permeabilization analysis and comparative immunoprecipitation studies with different anti-CD45 MAb from fractions enriched in various neutrophil granules revealed that CD45 polypeptides (180 and 130-150 kDa) from internal granules are antigenic and biochemically identical to those expressed on plasma membrane.

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“…The family of human leukocyte common antigens (LCA ; CD45) is composed of at least four glycoprotein members with molecular masses of 180,190,205, and 220 kD resulting from alternative splicing (1)(2)(3)(4). On the protein level, the heterogeneity of different CD45 isoforms can be resolved by mAbs that react with restricted epitopes specific for distinct isoforms .…”

mentioning

confidence: 99%

Genetically determined lack of CD45R- T cells in healthy individuals. Evidence for a regulatory polymorphism of CD45R antigen expression.

Schwinzer

Wonigeit

1990

The Journal of Experimental Medicine

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The family of human leukocyte common antigens (LCA ; CD45) is composed of at least four glycoprotein members with molecular masses of 180, 190, 205, and 220 kD resulting from alternative splicing (1-4). On the protein level, the heterogeneity of different CD45 isoforms can be resolved by mAbs that react with restricted epitopes specific for distinct isoforms . In humans, mAb UCHLI detects the CD45RO epitope specific for the low molecular mass isoform (180 kD) of CD45 ; several mAbs detect the CD45R epitope present only on the high molecular mass isoform (205 and 220 kD) (5-7) .The CD45R and CD45RO isoforms have been reported to define complementary subsets among CD4+ and CD8+ T cells (8) that differ in functional properties . Whereas CD45RO' T cells respond well to recall antigens such as tetanus toxoid, weak or no reactivity has been reported for CD45R+ T cells (5, 9). After in vitro activation, CD45R + T cells have been shown to lose CD45R antigens and to express CD45RO molecules (10-12). These results led to the assumption that expression of the CD45RO isoform and loss of CD45R molecules are typical features of primed or memory T cells (13,14). We now report on a genetically determined variant pattern of CD45R expression . Volume 171 May 1990 1803-1808 Materials and Methods Brief Definitive ReportBlood Donors and Cell Separation . Heparinized peripheral venous blood was taken from 52 male and female healthy individuals ; furthermore, three families were studied. PBMC were isolated by Ficoll gradient centrifugation .mAbs and Flow Cytometry. The low molecular mass isoform of LCA (180 kD) was detected by mAb UCHLI (CD45RO) (5), donated by Dr. P. C. L. Beverley, London, UK. The high molecular mass isoform (205 and 220 kD) was identified by mAb Heidelberg, FRG) and by several antibodies included in the CD45R panel of the Fourth Workshop of Leucocyte Typing (6). Common epitopes expressed on all isoforms of LCA were identified by mAb GRT2 . Binding of the various mAbs to the respective CD45 epitopes was detected by indirect immunofluorescence. Coexpression of high and low molecular mass isoforms of CD45 was analyzed by two-color flow cytometry using directly labeled FITC-Leu-18 in combination with indirect staining for UCHLI . PBMC were incubated with mAb

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Differential usage of three exons generates at least five different mRNAs encoding human leukocyte common antigens.

Cited by 305 publications

References 51 publications

Extracellular Isoforms of CD6 Generated by Alternative Splicing Regulate Targeting of CD6 to the Immunological Synapse

Extracellular Isoforms of CD6 Generated by Alternative Splicing Regulate Targeting of CD6 to the Immunological Synapse

Biochemical and antigenic characterization of CD45 polypeptides expressed on plasma membrane and internal granules of human neutrophils

Genetically determined lack of CD45R- T cells in healthy individuals. Evidence for a regulatory polymorphism of CD45R antigen expression.

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