Identification of an HLA-DQ6-derived peptide recognized by mouse MHC class I H-2Db-restricted CD8+ T cells in HLA-DQ6 transgenic mice |
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Authors: | Tsutao Takeshita Yoshinori Fukui Ken Yamamoto Kazuaki Yamane Takeshi Inamitsu Nobuhiro Kamikawaji Takehiko Sasazuki |
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Affiliation: | (1) Department of Genetics, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, 812 Fukuoka, Japan;(2) Department of Pediatrics, Kyushu University, 3-1-1 Maidashi, Higashi-ku, 812 Fukuoka, Japan |
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Abstract: | Summary CD8+ T cells from C57BL/6(B6) mice show cytotoxicity to B cell blasts prepared from syngeneic transgenic mice expressing HLA-DQ6 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 orβ 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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Keywords: | HLA-DQ6 transgenic mice CTL binding motifs peptide |
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