2003
DOI: 10.1097/01.asn.0000091588.80007.0e
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The Fine Specificity and Cytokine Profile of T-Helper Cells Responsive to the α3 Chain of Type IV Collagen in Goodpasture’s Disease

Abstract: Abstract. Goodpasture's disease is a severe nephritis characterized by autoantibodies to the ␣3 chain of type IV collagen, ␣3(IV)NC1, in the glomerular basement membrane. The disease is very strongly associated with HLA-DR15, the affinities of ␣3(IV)NC1 peptides for DR15 are known, and elution experiments have identified major naturally processed sequences. Here, the fine specificity and cytokine profile of ␣3(IV)NC1-reactive T cells from patients with Goodpasture's disease is defined. Peripheral blood mononuc… Show more

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Cited by 71 publications
(112 citation statements)
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“…Three major linear epitopes were identified with high frequencies of recognition: P14, P16, and P18. Second, a mutual T and B cell epitope, P14, was revealed in patients with anti-GBM disease, which was not only a target antigen of circulating antibodies found in this study but was also a formerly defined T cell epitope in Goodpasture patients (22). Third, the frequencies and levels of antibodies against linear epitopes were found, for the first time, to be associated with the severity of kidney injury of anti-GBM patients.…”
Section: Discussionsupporting
confidence: 52%
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“…Three major linear epitopes were identified with high frequencies of recognition: P14, P16, and P18. Second, a mutual T and B cell epitope, P14, was revealed in patients with anti-GBM disease, which was not only a target antigen of circulating antibodies found in this study but was also a formerly defined T cell epitope in Goodpasture patients (22). Third, the frequencies and levels of antibodies against linear epitopes were found, for the first time, to be associated with the severity of kidney injury of anti-GBM patients.…”
Section: Discussionsupporting
confidence: 52%
“…P14, amino acid residues 129-150, was formerly defined as a T cell epitope that could stimulate peripheral CD4 + T cell proliferation in Goodpasture patients (22). Previous studies have demonstrated that P14 contained the core sequence with highest predicted binding affinity with HLA-DR15 (25,26), which was proven to be the genetic marker for susceptibility to anti-GBM disease.…”
Section: Discussionmentioning
confidence: 99%
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“…These epitopes differed from those recently described in a human HLA-DRB1*15:01-restricted transgenic mouse model of anti-GBM disease and from T cell epitopes identified in HLA-DR15 + patients with Goodpasture's disease (7,21). Interestingly, P05 includes the dominant epitope found in the WKY rat EAG model (26)(27)(28).…”
Section: Discussionmentioning
confidence: 59%
“…Diagnosis is based on the detection of circulating autoantibodies and their deposition along the GBMs (3,4). The major autoantigen is the noncollagenous domain 1 of the a3-chain of type IV collagen (a3IV-NC1), which is targeted by both Abs and T cells (5)(6)(7). The role of the T cells in the initiation and progression of crescentic GN is still incompletely understood (8,9).…”
mentioning
confidence: 99%