کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2168008 | 1092368 | 2007 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Class I MHC allochimeric presentation of composite immunogenic and self epitopes induces tolerance to genetically diverse rat strains
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیولوژی سلول
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چکیده انگلیسی
Functional topography of rat class I major histocompatibility complex (MHC) molecule was studied. The α1-helical sequences that are shared by class I RT1.Al and RT1.Au were substituted in the RT1.Aa molecule to produce the composite [α1hl/u]-RT1.Aa MHC class I allochimeric molecule. Dominant immunogenic epitopes that induce accelerated rejection were identified within the hypervariable regions of the α1 domain of RT1.Aa, RT1.Al, and RT1.Au. Peri-transplant portal venous delivery of MHC class I allochimeric proteins, that included composite α1 helical immunodominant epitopes of RT1.Au and RT1.Al, induced donor-specific tolerance to RT1u (Wistar Furth, WF) and RT1l Lewis, LEW) disparate cardiac allografts in ACI (RT1a) 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-γ, 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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Immunology - Volume 248, Issue 1, July 2007, Pages 48-58
Journal: Cellular Immunology - Volume 248, Issue 1, July 2007, Pages 48-58
نویسندگان
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,