CD8+ T cells from C57BL/6(B6) mice show cytotoxicity to B cell blasts prepared from syngeneic transgenic mice expressing HLADQ6 molecules in a mouse MHC class I H-2Db restricted manner. Although these results suggest that CD8+ T cells recognize peptides derived from DQ6 molecule bound to H-2Db on target cells, no direct evidence so far has been obtained. To clarify this, we synthesized 23 peptides corresponding to DQ6α or β chain and carrying the motifs of Db-binding peptides, and examined their capacity to induce cytotoxicity in the CD8+ T cell line. We show here that DQA1-2, one of these peptides, induced cytotoxicity of the CD8+ T cells when this peptide was pulsed to H-2Db expressing target cells, as efficiently as HLA-DQ6 expressing target cells did. Thus, our results suggest that DQA1-2 can be naturally processed from DQ6 molecules and recognized by the CD8+ T cells in the context of H-2Db molecules. These results suggest that allogeneic HLA class II molecules are involved in the rejection not only as the ligand for T cell receptor of alloreactive CD4+ T cells but also as self-peptides bound to HLA class I molecules recognized by CD8+ T cells.
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