Format:
Online-Ressource
ISSN:
1521-4141
Content:
Abstract: Insulin‐dependent diabetes mellitus (IDDM) is an autoimmune disease with a predominantly non‐hereditary etiology that results in a destruction of pancreatic beta cells by autoaggressive T lymphocytes. Neither the mechanism of initial stimulation of these T cells nor the nature of the environmental factors implicated in the disease have so far been identified. However, both issues are taken into account by the hypothesis of initial T cell activation by viral or bacterial mimicry peptides with sequence similarities to pancreatic self antigens. We determined sequential epitope motifs to search for mimicry peptides stimulating T cell lines specific for two epitopes derived from the IDDM autoantigen 65‐kDa glutamic acid decarboxylase (GAD65). These were GAD65 (88 – 99), presented by HLA‐DRB1*0101, and GAD65 (248 – 257), presented by HLA‐DRB5*0101. T cell stimulation by peptides with substitutions in HLA anchor or T cell contact positions was analyzed to establish degenerate epitope motifs for database searching. Out of 28 tested candidate mimicry peptides derived from bacterial, viral and human proteins, 3 stimulated T cell lines and a T cell clone specific for epitope GAD65 (248 – 257). Our results demonstrate that mono‐ and polyclonal GAD65‐specific T cells from IDDM patients can be stimulated by viral and bacterial peptides with little apparent sequence homology with autoantigenic epitopes. Moreover, in a synopsis with related published studies, our findings suggest that simple degenerate search motifs comprising principal T cell contacts plus HLA class II binding motifs may suffice to identify most mimicry peptides.
In:
volume:28
In:
number:6
In:
year:2006
In:
pages:1902-1910
In:
extent:9
In:
European journal of immunology, Weinheim : Wiley-VCH, 1971-, 28, Heft 6 (2006), 1902-1910 (gesamt 9), 1521-4141
Language:
English
DOI:
10.1002/(SICI)1521-4141(199806)28:06〈1902::AID-IMMU1902〉3.0.CO;2-J
URN:
urn:nbn:de:101:1-2023112504070411834998
URL:
https://doi.org/10.1002/(SICI)1521-4141(199806)28:06〈1902::AID-IMMU1902〉3.0.CO;2-J
URL:
https://nbn-resolving.org/urn:nbn:de:101:1-2023112504070411834998
URL:
https://d-nb.info/1311119051/34
URL:
https://doi.org/10.1002/(SICI)1521-4141(199806)28:06〈1902::AID-IMMU1902〉3.0.CO;2-J
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