| Autor: |
Berschick, Peter, Fehsel, Karin, Weltzien, Hans Ulrich, Kolb, Hubert |
| Zdroj: |
Journal of Autoimmunity; August 1993, Vol. 6 Issue: 4 p405-422, 18p |
| Abstrakt: |
The repertoire of Vβ5 and Vβ8 T-cell receptors in pancreatic lesions of autoimmune diabetic NOD mice was analysed by sequencing the CDR3 and adjacent regions. T-cell receptor mRNA isolated from four different cell populations (i.e. spleen, lymph node, infiltrated islets from male and female NOD mice) was amplified by PCR and cloned; out of these, 339 clones were sequenced. Of 170 β chains sequenced from intra-islet T cells, nearly 90% were unique and six other sequences were found 2 to 4 times. These data argue against any oligoclonality of the islet infiltrate. Despite the lack of clonal restriction, we observed a bias in TcR usage which indicates the existence of some selective pressure with regard to TcR structure. Of the Vβ5 positive cells, 30% to 40% showed a rearrangement of Vβ5 to Jβ2.6 and a complete lack of Vβ5-Jβ1.6 combination. The selective Jβusage was not restricted to islets but was found in all tissues analysed. Vβ8 positive cells did not show such an overrepresentation of Vβ-Jβcombinations with the exception of clones of infiltrated islets of partially diabetes-resistant male NOD mice. There the rearrangement of Vβ8-Jβ1.1 was markedly over-expressed. Analysis of the CDR3 region did not show selection of specific TcR with regard to region length. However, we found a restricted use of amino acids in the second position of the CDR3 region. Vβ8 chains had conserved an aspartic acid from the germline configuration in about half of the cases in all tissues analysed. Vβ5 chains also showed diversity of position 2 but not islet specificity of rearrangements. Mutated chains had a clear bias towards proline indicating selective pressure in favour of this amino acid. |
| Databáze: |
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