ArticleBMC immunology2007
Use of molecular modeling and site-directed mutagenesis to define the structural basis for the immune response to carbohydrate xenoantigens.
Article in BMC immunology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
10 citing papers in PubMed, 18 citations in OpenAlex.
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- DeepImmuno: deep learning-empowered prediction and generation of immunogenic peptides for T-cell immunity.Briefings in bioinformatics · 2021Article
- Broad specificity of immune helminth scFv library to identify monoclonal antibodies targeting Strongyloides.Scientific reports · 2021Article
- DeepImmuno: Deep learning-empowered prediction and generation of immunogenic peptides for T cell immunity.bioRxiv : the preprint server for biology · 2020Article
- Improvement of thermal stability via outer-loop ion pair interaction of mutated T1 lipase from Geobacillus zalihae strain T1.International journal of molecular sciences · 2012Article
- Critical epitopes in the nucleocapsid protein of SFTS virus recognized by a panel of SFTS patients derived human monoclonal antibodies.PloS one · 2012Article
- The anti-nonGal xenoantibody response to alpha1,3-galactosyltransferase gene knockout pig xenografts.Current opinion in organ transplantation · 2010Review
- Immunoproteomic identification of bovine pericardium xenoantigens.Biomaterials · 2008Article
- The anti-non-gal xenoantibody response to xenoantigens on gal knockout pig cells is encoded by a restricted number of germline progenitors.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2008Article
- Xenoantibody response to porcine islet cell transplantation using GTKO, CD55, CD59, and fucosyltransferase multiple transgenic donors.XenotransplantationArticle
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundNatural antibodies directed at carbohydrates reject porcine xenografts. They are initially expressed in germline configuration and are encoded by a small number of structurally-related germline progenitors. The transplantation of genetically-modified pig organs prevents hyperacute rejection, but delayed graft rejection still occurs, partly due to humoral responses. IgVH genes encoding induced xenoantibodies are predominantly, not exclusively, derived from germline progenitors in the VH3 family. We have previously identified the immunoglobulin heavy chain genes encoding VH3 xenoantibodies in patients and primates. In this manuscript, we complete the structural analysis of induced xenoantibodies by identifying the IgVH genes encoding the small proportion of VH4 xenoantibodies and the germline progenitors encoding xenoantibody light chains. This information has been used to define the xenoantibody/carbohydrate binding site using computer-simulated modeling.
resultsThe VH4-59 gene encodes antibodies in the VH4 family that are induced in human patients mounting active xenoantibody responses. The light chain of xenoantibodies is encoded by DPK5 and HSIGKV134. The structural information obtained by sequencing analysis was used to create computer-simulated models. Key contact sites for xenoantibody/carbohydrate interaction for VH3 family xenoantibodies include amino acids in sites 31, 33, 50, 57, 58 and the CDR3 region of the IgVH gene. Site-directed mutagenesis indicates that mutations in predicted contact sites alter binding to carbohydrate xenoantigens. Computer-simulated modeling suggests that the CDR3 region directly influences binding.
conclusionXenoantibodies induced during early and delayed xenograft responses are predominantly encoded by genes in the VH3 family, with a small proportion encoded by VH4 germline progenitors. This restricted group can be identified by the unique canonical structure of the light chain, heavy chain and CDR3. Computer-simulated models depict this structure with accuracy, as confirmed by site-directed mutagenesis. Computer-simulated drug design using computer-simulated models may now be applied to develop new drugs that may enhance the survival of xenografted organs.
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