Cross-reactivity of a normal human cell surface antigen with primate retrovirus glycoproteins

Purcell, Damian

doi:10.1016/0198-8859(85)90015-1

Cited by 12 publications

(5 citation statements)

References 19 publications

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“…Antisera to the envelope gp70 glycoproteins of the gibbon ape leukaemia virus (GaLV) (the closest primate relative of MuLV) and the Mason Pfizer monkey virus (MPMV), but not to baboon endogenous virus (BaEV) or simian sareoma viruses (SSV/SSAV), cross-react with CD46. Furthermore, the E4 3 MoAb reacts with GaLV and MPMV gp70 molecules (3). Together these findings suggest that CD46 may share a functional epitope with retroviral gp70, or that CD46 may itself be a gp70 molecule encoded by a human endogenous retrovirus.…”

Section: Introductionmentioning

confidence: 81%

“…The human cell surface antigen CD46 shares antigenic determinants with GaLV and MPMV envelope gp70 molecules (3). To understand the specificity and significance of this cross-reactivity it was important to determine whether the cross-reactive epitope to which the E4 3 MoAb binds involves carbohydrate, or protein alone.…”

Section: Discussionmentioning

confidence: 99%

“…First, the CD46 from human cells could be passively introduced into the retroviral envelope during budding from the plasma membrane of CD46"*' host cells used in the culture of the GaLV and MPMV retroviruses (4). As shown previously, this mechanism cannot explain this phenomenon because the CD46 status of the retroviral host cells often does not correlate with the observed pattern of cross-reactivity (3). Second, the cross-reactivity between CD46 and GaLV and MPMV gp70 may arise from a common carbohydrate moiety shared by these glycoproteins; carbohydrate is added to the viral gp70 by host-specific mechanisms (5) and therefore only coincidentally associated with the retroviral particles.…”

Section: Introductionmentioning

confidence: 91%

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The human non‐lineage antigen CD46 (HuLy‐m5) and primate retroviral gp70 molecules share protein‐defined antigenic determinants

Purcell

Deacon

1989

Immunol Cell Biol

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SummaryThe CD46 lymphocyte surface antigen of man (until recently called HuLy-m5), and defined by the E4-3 monoclonal antibody (MoAb), shares cross-reactive antigenic epitopes with the envelope gp70 glycoproteins of gibbon ape leukaemia virus (GaLV) and Mason Pfizer monkey virus (MPMV) primate rctroviruses. It is now shown that the cross-reactive antigenic epitope shared by these three molecules is determined solely by the protein portion of these glycoproteins, and that the A'-linked and O-linked carbohydrate moieties of these glycoproteins do not directly or sterically contribute to the antigenic cross-reactivity. When CD46 molecules (mol.wt = 66 and 56 kDa) from human thymocytes were stripped of sialic acid with neuraminidase, or stripped of A'-linked carbohydrate with endoglycosidase F, the E4-3 MoAb was still able to bind and immunoprecipitate the protein core of CD46 (mol.wt = 56 and 44 kDa). Similarly, polyclonal antisera to GaLV and MPMV precipitated deglycosylated CD46, although at a reduced efficiency. The cross-reacting E43 MoAb, anti-GaLV and anti-MPMV antisera also immunoprecipitated HuLy-m5 primary translation protein lacking A' -or O-linked carbohydrate from the in vitro translation products of human thymocyte mRNA. Thus, the antigenic cross-reactivity of CD46 molecules with GaLV gp70 and MPMV gp70 is both specific and due to protein structure rather than to carbohydrate; the findings suggest that retrovinises may have acquired a functional epitope from human CD46 or that an endogenous retroviral sequence of human may partially or completely encode the CD46 antigen.

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Section: Introductionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 91%

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The human non‐lineage antigen CD46 (HuLy‐m5) and primate retroviral gp70 molecules share protein‐defined antigenic determinants

Purcell

Deacon

1989

Immunol Cell Biol

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“…1). A 74-kDa isoform (termed y) was observed in EBV-transformed B cells (lane 5) and two of the three leukemic samples (lanes 8,10). Lymphocytes from healthy donors and cells from leukemic patients contained CD46 isoforms that resolved into two major clusters of bands at 66-and 56-kDa (termed Most transcripts were derived from the alternative splicing of exons 8,9,12 and 13 [12,13] shown in Figs.…”

Section: Tissue-specific Expression Of Cd46 Protein Isoformsmentioning

confidence: 97%

Tissue‐specific and allelic expression of the complement regulator CD46 is controlled by alternative splicing

1992

Self Cite

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CD46 (membrane cofactor protein) is a human cell surface glycoprotein with cofactor activity for factor I-mediated cleavage of complement components C3b and C4b. The CD46 protein from normal lymphocytes resolves on sodium dodecyl sulfate-polyacrylamide gel electrophoresis as two major bands of 66 and 56 kDa. CD46 cDNA encodes four extracellular short consensus repeat domains, a Ser/Thr/Pro (STP)-rich region, a transmembrane region and a cytoplasmic tail. We now show that exquisite control of mRNA splicing is responsible for the heterogeneous expression of CD46 isoforms. Differential splicing of 5 exons generates at least 14 CD46 mRNA variants whose expression is stringently regulated by allelic, tissue-specific and malignancy-related factors, as: (a) leukemic cells and Epstein-Barr virus-transformed B cells preferentially incorporate the first of three STP exons (exon 7) into mRNA, and produce a larger CD46 isoform of 74 kDa, (b) an allelic difference in the proportion of 66- and 56-kDa CD46 isoforms on lymphocytes corresponds to the preferential inclusion or exclusion of the second STP exon (exon 8), (c) the third STP exon (exon 9) is specifically deleted in some placentae, (d) spermatozoa delete both exons 12 and 13, encoding a shorter transmembrane region and a unique cytoplasmic tail and (e) all tissues tested differentially splice exon 13, resulting in two alternative cytoplasmic tails. The distribution of the 14 alternatively spliced RNA transcripts correlated with the presence of protein isoforms of the predicted size, indicating that alternative splicing leads to heterogeneity of CD46 glycoproteins.

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“…In SLE two unidentified components with approximately the same molecular weights have been detected in CIC 6. Antisera against animal retroviral glycoproteins react with normal human cell surface components 22 23. The reaction of the anti-gp7O antiserum, however, was restricted to CIC from three of the patients, which indicates that the 70 kD antigen is not a normal cellular component cosedimenting with the CIC during sucrose gradient centrifugation.The anti-gp7O antiserum reacted with a 40-45 kD component in addition to a 70 kD component.…”

mentioning

confidence: 92%

Analysis of circulating immune complexes from patients with ankylosing spondylitis by gel electrophoresis and immunoblotting using antiserum against a psoriasis associated retrovirus-like particle.

Rødahl¹,

Iversen²

1986

Annals of the Rheumatic Diseases

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SUMMARY Circulating immune complexes (CIC) were isolated from patients with ankylosing spondylitis (AS) and healthy blood donors by isopycnic ultracentrifugation in sucrose gradients. The CIC were analysed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting. The major components of the CIC were identified as albumin, immunoglobulins, and complement factors. A 70 kD component and several low molecular weight components (Mr 19 kD and 14 kD (doublet)) were detectable only in CIC from patients with AS. An antiserum raised against the envelope glycoprotein, gp7O, of a psoriasis associated retrovirus-like particle was applied to check for cross reacting activity. This antiserum reacted with both a 70 kD and a 40-45 kD component in CIC from three out of six patients but not with CIC from any of the blood donors.

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Cross-reactivity of a normal human cell surface antigen with primate retrovirus glycoproteins

Cited by 12 publications

References 19 publications

The human non‐lineage antigen CD46 (HuLy‐m5) and primate retroviral gp70 molecules share protein‐defined antigenic determinants

The human non‐lineage antigen CD46 (HuLy‐m5) and primate retroviral gp70 molecules share protein‐defined antigenic determinants

Tissue‐specific and allelic expression of the complement regulator CD46 is controlled by alternative splicing

Analysis of circulating immune complexes from patients with ankylosing spondylitis by gel electrophoresis and immunoblotting using antiserum against a psoriasis associated retrovirus-like particle.

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