| Autor: |
de Koster HS; Department of Immunohematology and Blood Bank, University Hospital Leiden, The Netherlands., Vermeulen CJ, Koning F |
| Jazyk: |
angličtina |
| Zdroj: |
Tissue antigens [Tissue Antigens] 1998 Jan; Vol. 51 (1), pp. 88-95. |
| DOI: |
10.1111/j.1399-0039.1998.tb02951.x |
| Abstrakt: |
Rejection of transplants is frequently caused by activation of alloreactive T cells that recognize HLA/peptide differences between patient and graft. This T-cell response can be directed towards the HLA molecule, the HLA-bound peptide or towards a combination. More insight in the involvement of peptides in this process may help to find ways to avoid rejection using for example antagonist peptides. In recent years many naturally processed HLA-bound peptides have been identified. This raises the question of whether these, presumably abundant, peptides are involved in class II-specific allorecognition. To investigate this, we first determined the proportion of peptide-specific alloreactive T cells in the alloresponse against HLA-DR3. For this purpose we have tested a panel of DR3-specific alloreactive T-cell clones against a DM-mutant (i.e. peptide loading deficient) cell line. We found that 59 out of 64 alloreactive T-cell clones were dependent upon the presence of DM for an optimal response. However, only 2 DM-dependent T-cell clones recognize known peptide sequences. Thus we conclude that most DR3-specific alloreactive T-cell clones are peptide specific and that the currently known DR3-bound peptides are not the main target for allorecognition. Finally, we identified 4 T-cell clones that recognized the DM-mutant better than the wild-type cell line. The response against the wild-type cell line could not be restored with invariant chain derived peptides (CLIP). This provides additional evidence that DM can negatively select self-peptides other than CLIP, which can result in selection against peptides involved in allorecognition. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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