Class I MHC allochimeric presentation of composite immunogenic and self epitopes induces tolerance to genetically diverse rat strains.

Class I MHC allochimeric presentation of composite immunogenic and self epitopes induces tolerance to genetically diverse rat strains. Research Abstract Details 

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Class I MHC allochimeric presentation of composite immunogenic and self epitopes induces tolerance to genetically diverse rat strains. Abstract Text:

Natalya V Semiletova,Xiu-Da Shen,Daniel M Feldman,Feng Gao,Ana Mhoyan,Dhai Liu,Ronald W Busuttil,Jerzy W Kupiec-Weglinski,Rafik M Ghobrial,Natalya V Semiletova,Xiu-Da Shen,Daniel M Feldman,Feng Gao,Ana Mhoyan,Dhai Liu,Ronald W Busuttil,Jerzy W Kupiec-Weglinski,Rafik M Ghobrial,

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.

Class I MHC allochimeric presentation of composite immunogenic and self epitopes induces tolerance to genetically diverse rat strains. Publishing Authors By Initials

NV Semiletova,XD Shen,DM Feldman,F Gao,A Mhoyan,D Liu,RW Busuttil,JW Kupiec-Weglinski,RM Ghobrial,NV Semiletova,XD Shen,DM Feldman,F Gao,A Mhoyan,D Liu,RW Busuttil,JW Kupiec-Weglinski,RM Ghobrial,

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Class I MHC allochimeric presentation of composite immunogenic and self epitopes induces tolerance to genetically diverse rat strains. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Cellular immunology

VOLUME: 248

Page Numbers: 48-58

Journal Abbreviation: Cell. Immunol.

ISSN: 1090-2163

DAY: 23

MONTH: 10

YEAR: 2007

Class I MHC allochimeric presentation of composite immunogenic and self epitopes induces tolerance to genetically diverse rat strains. Information

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LANGUAGE: eng

NlmUniqueID: 1246405

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Grant and Affiliation Information for Class I MHC allochimeric presentation of composite immunogenic and self epitopes induces tolerance to genetically diverse rat strains.

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.

Country: United States

AGENCY: United States NIAID

GRANT: R01 AI49945

ACRONYM: AI

MEDLINETA: Cell Immunol

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