Rejection of transplants is frequently caused by activation of alloreactive T cells that recognize HLA/peptide differences between @entity1 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- @entity4106 . For this purpose we have tested a panel of @entity4106 -specific alloreactive T-cell clones against a @entity3918 -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 @entity3918 for an optimal response. However, only 2 @entity3918 -dependent T-cell clones recognize known peptide sequences. Thus we conclude that most @entity4106 -specific alloreactive T-cell clones are peptide specific and that the currently known @entity4106 -bound peptides are not the main target for allorecognition. Finally, we identified 4 T-cell clones that recognized the @entity3918 -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 @entity3918 can negatively select self-peptides other than CLIP, which can result in selection against peptides involved in allorecognition.

The majority of HLA- @entity4106 alloreactive T cells is peptide specific, but does not recognize known XXXX -bound sequences.

@entity1 :: ('9606', 'Species') :: ['patient'] @entity3918 :: ('MESH:D009223', 'Disease') :: ['DM'] @entity4106 :: ('8718', 'Gene') :: ['DR3']
@entity4106 :: (8718,Gene) :: ['DR3']
