Cloning and Characterization of Human Erythroid Membrane-Associated Protein, Human ERMAP

Xu, Hongxia; Foltz, Lisa; Sha, Michael Y.; Madlansacay, Mary Rose; Cain, Carol A.; Lindemann, Garrett W.; Vargas, Joseph A.; Nagy, Dea; Harriman, Bill; Mahoney, Walt; Schueler, Paula A.

doi:10.1006/geno.2001.6600

Cited by 29 publications

(21 citation statements)

References 7 publications

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“…MOG is expressed within the immunologically privileged environment of the CNS where it is sequestered from normal lymphocyte trafficking and unable to trigger antigen-specific B cell tolerance. The composition of the anti-MOG B cell repertoire, however, can be influenced by other self-antigens (37), which may include homologous proteins such as butyrophilin (41) or erythroid membrane-associated protein (42), the N-terminal IgV-like domains of which exhibit sequence identities to MOG Igd of 45-55% (43). Strikingly, those residues bound by 8-18C5, an antibody that has escaped this tolerogenic influence, are least conserved between MOG and its relatives (Fig.…”

Section: Resultsmentioning

confidence: 99%

Structural insights into the antigenicity of myelin oligodendrocyte glycoprotein

Breithaupt

Schubart

Zander

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

123

120

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M ultiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of the central nervous system (CNS) associated with autoaggressive T and B cell responses to various myelin proteins. Myelin oligodendrocyte glycoprotein (MOG) was identified as a candidate autoantigen in MS because it induces a demyelinating antibody response in laboratory animals with experimental autoimmune encephalomyelitis (EAE), an animal model of MS (1). MOG is a quantitatively minor type I transmembrane CNS protein of unknown function with a single extracellular Ig-like domain (2). In contrast to other CNS proteins, MOG is found only in mammals and is highly conserved across species. It is expressed exclusively in the CNS by myelin-forming oligodendrocytes and is preferentially localized at the outermost surface of the myelin sheath thus directly exposed to autoantibodies in the extracellular milieu. MOG is the only antigen that can induce both a pathogenic demyelinating autoantibody response and an encephalitogenic T cell response in experimental animals (3). In MOG-induced EAE this combination of immune effector mechanisms reproduces the demyelinating pathology seen in the majority of patients with MS. The clinical relevance of autoimmune responses to MOG in MS is supported by reports that MS is associated with enhanced MOG-specific T and B cell responses and by the identification of MOG-specific antibodies associated with myelin debris in actively demyelinating MS lesions (4). Experimental evidence indicates that the autoantibody response to MOG is heterogeneous; demyelinating MOG-specific autoantibodies recognize purely conformation-dependent epitopes whereas MOG peptide-specific antibodies fail to recognize the native protein (5-7). To examine the structural basis of the pathogenic autoantibody response to MOG we determined the crystal structures of the extracellular domain of rat MOG (residues 1-126, MOG Igd ) and a complex of MOG Igd with the chimeric antigen-binding fragment (Fab) of the demyelinating MOG-specific monoclonal antibody 8-18C5 (8). Materials and Methods Preparation of Recombinant MOG Igd and the MOG Igd -(8-18C5)-FabComplex. The cDNA of the extracellular domain of rat MOG (residues 1-125) was subcloned into the His-tag expression vector pQE-12. The protein was overexpressed in inclusion bodies in Escherichia coli, refolded, and further purified by nickel-nitrilotriacetic acid affinity chromatography and gel filtration. Selenomethionine (SeMet)-labeled protein was produced in the methionine-auxotrophic E. coli strain B834(DE3) and grown in minimal medium with SeMet (0.3 mM) substituted for methionine. The cDNA of the variable domains of the mouse monoclonal antibody 8-18C5 was subcloned into the expression vector pASK107, yielding the chimeric (8-18C5)-Fab composed of the 8-18C5 variable domains, the human IgG constant domains, and the Strep tag II fused to the C terminus of the heavy chain (9, 10). (8-18C5)-Fab was produced by periplasmic secretion in E. coli and purified by streptavidin affinity chromatogr...

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Section: Resultsmentioning

confidence: 99%

Structural insights into the antigenicity of myelin oligodendrocyte glycoprotein

Breithaupt

Schubart

Zander

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

123

120

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“…The chromosomal position of the ERMAP gene and the molecular weight of the encoded ERMAP protein matched the data closely that were previously established for the Scianna glycoprotein. 22,23 These observations prompted us to explore whether ERMAP alleles were underlying the Scianna antigens.…”

Section: Resultsmentioning

confidence: 99%

“…8 ERMAP was expressed on RBCs 22,23 and shared homology to chicken blood group antigens. 23 The molecular weight of 60 to 68 kD determined for the glycosylated Scianna protein 11 was compatible with 446 amino acids predicted for the mature ERMAP protein.…”

Section: Discussionmentioning

confidence: 99%

“…The ERMAP protein is believed to represent an adhesion protein and possesses a C1q recognition sequence. 22,23 It is characterized by the presence of an extracellular immunoglobulin domain and an intracellular B30.2 domain. The immunoglobulin domain is most similar to myelin/ oligodendrocyte glycoprotein (MOG), a component of the myelin sheath on the surface of oligodendrocytes and Schwann cells and is a common autoantigen in patients with multiple sclerosis.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, the ERMAP alleles encoding a His at position 26 carried a C at position 54 (allele frequency 0.67) and represented the wild-type allele. 22,23 …”

Section: Population Frequencies Of the Ermap (His26tyr) Allele And Thmentioning

confidence: 99%

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Scianna antigens including Rd are expressed by ERMAP

Wagner

Poole

Flegel

2003

Blood

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The Scianna blood group encompasses the high-frequency antigens Sc1 and Sc3 and the low-frequency antigen Sc2. Another lowfrequency antigen Rd (Radin) was suggested to belong to the Scianna blood group. The molecular basis of the Scianna blood group was unknown. The erythrocyte membrane-associated protein (ERMAP) shared the genomic location, protein product size, and localization to the red blood cell (RBC) membrane surface with Scianna. The ERMAP gene was sequenced in probands with known Scianna and Radin phenotypes. In a Sc:-1,-2 proband, only an ERMAP allele with a 2-bp deletion in exon 3 causing a frameshift could be detected. A Sc:-1,2 proband was homozygous for the ERMAP(Gly57Arg) allele. An Rd ؉ proband was heterozygous for the ERMAP(Pro60Ala) allele. Polymerase chain reaction with sequence-specific priming (PCR-SSP) systems was developed to detect the Sc2 and Rd alleles of the ERMAP gene. The 2 alleles occurred with about 1% and less than 1% frequency in the population, which was compatible with the frequency of the Sc2 and Rd antigens known in whites. Two Sc2 ؉ and one Rd ؉ samples that were found by genotyping were confirmed by serology.

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Scianna Blood Group System

Daniels

2013

Human Blood Groups

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Cloning and Characterization of Human Erythroid Membrane-Associated Protein, Human ERMAP

Cited by 29 publications

References 7 publications

Structural insights into the antigenicity of myelin oligodendrocyte glycoprotein

Structural insights into the antigenicity of myelin oligodendrocyte glycoprotein

Scianna antigens including Rd are expressed by ERMAP

Scianna Blood Group System

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