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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2007-11-20
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pubmed:abstractText |
Functional topography of rat class I major histocompatibility complex (MHC) molecule was studied. The alpha1-helical sequences that are shared by class I RT1.A(l) and RT1.A(u) were substituted in the RT1.A(a) molecule to produce the composite [alpha(1h)(l/u)]-RT1.A(a) MHC class I allochimeric molecule. Dominant immunogenic epitopes that induce accelerated rejection were identified within the hypervariable regions of the alpha1 domain of RT1.A(a), RT1.A(l), and RT1.A(u). Peri-transplant portal venous delivery of MHC class I allochimeric proteins, that included composite alpha1 helical immunodominant epitopes of RT1.A(u) and RT1.A(l), induced donor-specific tolerance to RT1(u) (Wistar Furth, WF) and RT1(l) Lewis, LEW) disparate cardiac allografts in ACI (RT1(a)) hosts. Allochimeric generated tolerance was characterized by absence of T cell deletion or anergy. Donor specific IgM allo-Abs was not detected, while IgG alloresponse was markedly attenuated in sera of tolerant hosts. Further, long-term allografts in allochimeric-conditioned hosts exhibited moderate B cell infiltration when compared to rejecting controls. Analysis of intragraft cytokines revealed selective upregulation of IL-10 and marked inhibition of IL-2, IFN-gamma, and IL-4. Our findings indicate the emergence of a peripherally induced tolerant state, afforded by the novel approach of soluble class I allochimeric conditioning that presents donor immunogenic epitopes in the context of recipient class I determinants.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Histocompatibility Antigens Class I,
http://linkedlifedata.com/resource/pubmed/chemical/Immunodominant Epitopes,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin G,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin M,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-10,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-2,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-4,
http://linkedlifedata.com/resource/pubmed/chemical/Isoantigens,
http://linkedlifedata.com/resource/pubmed/chemical/Mutant Chimeric Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1090-2163
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
248
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
48-58
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:17936255-Animals,
pubmed-meshheading:17936255-Genetic Variation,
pubmed-meshheading:17936255-Graft Rejection,
pubmed-meshheading:17936255-Graft Survival,
pubmed-meshheading:17936255-Heart Transplantation,
pubmed-meshheading:17936255-Histocompatibility Antigens Class I,
pubmed-meshheading:17936255-Immune Tolerance,
pubmed-meshheading:17936255-Immunodominant Epitopes,
pubmed-meshheading:17936255-Immunoglobulin G,
pubmed-meshheading:17936255-Immunoglobulin M,
pubmed-meshheading:17936255-Immunohistochemistry,
pubmed-meshheading:17936255-Injections, Intravenous,
pubmed-meshheading:17936255-Interferon-gamma,
pubmed-meshheading:17936255-Interleukin-10,
pubmed-meshheading:17936255-Interleukin-2,
pubmed-meshheading:17936255-Interleukin-4,
pubmed-meshheading:17936255-Isoantigens,
pubmed-meshheading:17936255-Major Histocompatibility Complex,
pubmed-meshheading:17936255-Mutant Chimeric Proteins,
pubmed-meshheading:17936255-Rats,
pubmed-meshheading:17936255-Rats, Inbred ACI,
pubmed-meshheading:17936255-Rats, Inbred BN,
pubmed-meshheading:17936255-Rats, Inbred Lew,
pubmed-meshheading:17936255-Rats, Inbred WF,
pubmed-meshheading:17936255-Recombinant Fusion Proteins,
pubmed-meshheading:17936255-Sequence Alignment,
pubmed-meshheading:17936255-Species Specificity,
pubmed-meshheading:17936255-Transplantation, Homologous,
pubmed-meshheading:17936255-Transplantation Conditioning
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pubmed:year |
2007
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pubmed:articleTitle |
Class I MHC allochimeric presentation of composite immunogenic and self epitopes induces tolerance to genetically diverse rat strains.
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pubmed:affiliation |
The Dumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, 77-120 CHS, Los Angeles, CA 90095-7054, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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