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Molecular mimicry and systemic lupus...

Sim, Davis Lok.

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Molecular mimicry and systemic lupus erythematosus.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Molecular mimicry and systemic lupus erythematosus./
Author:	Sim, Davis Lok.
Description:	124 p.
Notes:	Adviser: Shu Man Fu.
Contained By:	Dissertation Abstracts International68-12B.
Subject:	Biology, Microbiology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3294817
ISBN:	9780549396673

Molecular mimicry and systemic lupus erythematosus.
Sim, Davis Lok.

Molecular mimicry and systemic lupus erythematosus. - 124 p.

Adviser: Shu Man Fu.

Thesis (Ph.D.)--University of Virginia, 2008.

This dissertation demonstrates the potential of T cell epitope mimicry to initiate autoimmune responses against lupus-associated antigens. This has important implications in the pathogenesis of SLE.

ISBN: 9780549396673Subjects--Topical Terms:

1017734
Biology, Microbiology.

Molecular mimicry and systemic lupus erythematosus.
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020 $a 9780549396673
035 $a (UMI)AAI3294817
035 $a AAI3294817
040 $a UMI $c UMI
100 1 $a Sim, Davis Lok. $3 1267764
245 1 0 $a Molecular mimicry and systemic lupus erythematosus.
300 $a 124 p.
500 $a Adviser: Shu Man Fu.
500 $a Source: Dissertation Abstracts International, Volume: 68-12, Section: B, page: 7918.
502 $a Thesis (Ph.D.)--University of Virginia, 2008.
520 $a This dissertation demonstrates the potential of T cell epitope mimicry to initiate autoimmune responses against lupus-associated antigens. This has important implications in the pathogenesis of SLE.
520 $a Systemic lupus erythematosus (SLE) is a complex, chronic autoimmune disease that presents itself with a diverse array of clinical manifestations. One of the hallmarks of SLE is the production of antibodies against a number of self-antigens. In particular, autoantibodies reactive against Sm proteins are considered to be more specific for systemic lupus erythematosus and are considered as a diagnostic criterion. One of the hypotheses behind the initiation of an immune response against Sm autoantigens is molecular mimicry between foreign and self proteins. Previous work has focused on molecular mimicry at the B cell level. However, clear evidence for this at the T cell level is lacking. This dissertation was designed to determine the role of T cell epitope mimicry in initiation of an immune response against SmD.
520 $a The first part of this dissertation deals with mapping of HLA-DR restricted T epitopes on Sm proteins. Due to the significant association between SLE patients and ITLA-DR3 or DR2, we have utilized HLA-DR tg mice as an experimental model system. Notably, multiple regions on SmD were identified as containing a HLA-DR3 restricted T epitope, with region 71-95 showing the highest IFN-gamma production. Using T-T hybridomas, this region was further narrowed to 79-93. Critical residues involved in either TCR contact or MHC binding were then identified. By characterizing the HLA-DR3 restricted T epitopes on SmD, we have identified targets for further studies into T cell mimicry.
520 $a The second part of this dissertation concentrates on identifying T cell mimics capable of initiating an anti-Sm antibody response. We have identified a peptide from galactoside ABC transporter protein from Vibrio bacteria as being capable of initiating an anti-SmD antibody response following immunization of HLA-DR3 tg mice. Antibodies against SmD were non-cross reactive against the immunogen, indicating activation of SmD-reactive T cells following immunization with the mimic. This was further supported by proliferation of T cells against SmD following immunization with the mimic.
590 $a School code: 0246.
650 4 $a Biology, Microbiology. $3 1017734
650 4 $a Health Sciences, Immunology. $3 1017716
690 $a 0410
690 $a 0982
710 2 $a University of Virginia. $3 645578
773 0 $t Dissertation Abstracts International $g 68-12B.
790 $a 0246
790 1 0 $a Fu, Shu Man, $e advisor
791 $a Ph.D.
792 $a 2008
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3294817