Adult and neonatal anti‐Gal response in knock‐out mice for α1,3galactosyltransferase

@article{LaTemple1998AdultAN,
  title={Adult and neonatal anti‐Gal response in knock‐out mice for $\alpha$1,3galactosyltransferase},
  author={Denise C. LaTemple and Uri Galili},
  journal={Xenotransplantation},
  year={1998},
  volume={5}
}
ABSTRACT: The knockout mouse to αl,3galactosyltransferase (αl,3GT KO) lacks the ability to synthesize α‐gal epitopes (Galα1,3Galβ1,4GlcNAc‐R) and is capable of producing low amounts of the natural anti‐Gal antibody. The present study indicates that repeated immunization of these mice with rabbit red blood cell (RRBC) membranes results in production of anti‐Gal in titers and specificity similar to those in humans. In contrast, immunized wild‐type mice completely lack anti‐Gal. Anti‐Gal in the α1… 
α1,3Galactosyltransferase knockout pigs produce the natural anti‐Gal antibody and simulate the evolutionary appearance of this antibody in primates
TLDR
Evaluating anti‐Gal prodution in α1,3GT knockout (GT‐KO) pigs recently generated from wild‐type pigs in which the α‐gal epitope is a major self‐antigen found it of interest to determine whether ancestral Old World primates could produce anti‐ Gal once α‐Gal epitopes were eliminated.
Distribution of, and immune response to, chicken anti‐αGal immunoglobulin Y antibodies in wild‐type and αGal knockout mice
TLDR
Results show that IgY binds to αGal epitopes in the WT mice and is cleared sometime over a 24‐hr time period and is an expected immunogen in mice eliciting a rather typical anti‐IgY IgM and IgG response.
Tolerization of Galα1,3Gal‐reactive B cells in pre‐sensitized α1,3‐galactosyltransferase‐deficient mice by nonmyeloablative induction of mixed chimerism
TLDR
The absence of B cells with receptors recognizing Gal in mixed chimeras suggests a role for clonal deletion/receptor editing in the maintenance of B cell tolerance.
Characteristics of α-Gal epitope, anti-Gal antibody, α1,3 galactosyltransferase and its clinical exploitation (Review)
TLDR
Targeting anti-Gal-mediated autologous tumor vaccines, which express α-Gal epitope to antigen-presenting cells, would increase their immunogenicity and elicit an immune response, which will be potent enough to eradicate the residual tumor cells.
Anti-gal antibodies in humans and 1, 3α-galactosyltransferase knock-out mice
TLDR
It is demonstrated that anti-GAL antibodies from immunized GALT/KO mice bind alphaGAL with an avidity/affinity similar to human anti- GAL antibodies and are able to induce hyperacute rejection of GAL+ heart allografts.
Sequential Analysis of Anti‐αGal Natural Antibody‐Producing B Cells in GalT Knockout Mice in Cyclophosphamide‐Induced Tolerance
TLDR
The authors' drug‐induced tolerance protocols are effective to induce tolerance in recipients that produce anti‐donor nAb, and the clonal destruction in the early stage and theClonal anergy or ignorance in the late stage after conventional conditioning with RRBC and CP.
The natural anti-Gal antibody.
TLDR
This chapter describes the studies which have led to the identification of the unique specificity of this antibody, the mechanisms inducing production and regulating its affinity, the genes encoding this antibodies, and the effects of immune tolerance on anti-Gal specificity.
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TLDR
These mice confirm the importance of the galactose alpha(1,3)-galactose epitope in human xenoreactivity and the logic of continuing efforts to generate pigs that lack this epitope as a source of donor organs.
Anti-pig IgM antibodies in human serum react predominantly with Gal(alpha 1-3)Gal epitopes.
TLDR
It is shown that most of human IgM antibodies present in the serum of healthy donors and reactive with pig cells react with galactose in an (alpha 1-3) linkage with Galactose--i.e., Gal(alpha 1,3)Gal.
Evolutionary relationship between the natural anti-Gal antibody and the Gal alpha 1----3Gal epitope in primates.
TLDR
The observed in vivo binding of anti-Gal to human normal senescent and some pathologic erythrocytes implies that the Gal alpha 1----3Gal epitope is present in man in a cryptic form.
Oocyte Galα1,3Gal Epitopes Implicated in Sperm Adhesion to the Zona Pellucida Glycoprotein ZP3 Are Not Required for Fertilization in the Mouse (*)
TLDR
The observations indicate that the Galα13Gal moiety is not essential to sperm-oocyte interactions leading to fertilization or to essentially normal development, and suggest that α1,3GT (−/−) mice will find utility for exploring approaches to diminish anti-Gal-dependent hyperacute xenograft rejection.
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A new natural anti-alpha-galactosyl IgG antibody (anti-Gal) was found to be present in high titer in the serum of every normal individual studied, suggesting a physiological role for this natural antibody in the aging of RBC.
Man, apes, and Old World monkeys differ from other mammals in the expression of alpha-galactosyl epitopes on nucleated cells.
TLDR
A striking evolutionary pattern in the expression of alpha-galactosyl epitopes on mammalian nucleated cells is observed, and an anomalous activity of this enzyme in man may result in initiation of autoimmune diseases because of the de novo expression of Gal alpha 1----3Gal beta 1----4GlcNAc-R epitopes recognized by anti-Gal.
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TLDR
Findings provide strong evidence that the Abs that accumulate in New World monkey organs during perfusion with baboon blood are the same Abs that would accumulate in a porcine organ transplanted into a primate and suggest that hyperacute rejection is not necessarily a reflection of phylogenetic distance but that the expression of terminal alpha-Gal residues provides an adequate target to initiate that process.
Distribution of Gal.alpha.1.fwdarw.3Gal.beta.1.fwdarw.4GlcNAc residues on secreted mammalian glycoproteins (thyroglobulin, fibrinogen, and immunoglobulin G) as measured by a sensitive solid-phase radioimmunoassay
TLDR
The evolutionary pattern of Gal alpha 1----3Gal beta 1----4GlcNAc residue distribution in in vivo secreted glycoproteins is similar to that observed in membranes of cell lines and of red cells.
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