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アクティブボード・２００２年 ７月
研究発表を行った学会；The 13th International Congress of Histocompatibility and Immunogenetics. Seattle, WA, USA, 18-20 May 2002
タイトル；A Single T Cell Receptor-Mediated Recognition of an Identical Peptide in The Context of Multiple HLA Molecules.
発表者；上野 貴将 氏
（エイズ学研究センター ウイルス制御分野）
Abstract；
A dual specific cytotoxic T lymphocyte (CTL) clone, recognizing an HIV Pol-derived peptide presented endogenously on both HLA-B*3501 and -B*5101 was established from an HIV infected patient having both HLA-B35 and -B51. Since the CTL clone had two in-frame alpha and one beta transcripts of the T cell receptor (TCR)-encoding genes, we employed a retrovirus mediated TCR transfer of individual alpha and beta chains to TCR-negative hybridoma to ask whether the two TCR complexes were responsible for the dual recognition or one complex. The results revealed that the Va12.1 TCR in complexed with Vb5.6 played a role in the peptide specific response in the context of both HLA-B*3501 and -B*5101 molecules. Another TCR alpha chain did not somehow result in surface expression on the transduced cells. Remarkably, the Va12.1/Vb5.6 TCR also recognized the same peptide when the peptide was presented on other allogeneic HLA molecules, such as HLA-B*5301 and -B*0702, that share the similar peptide-binding motifs. Moreover, the parental CTL clone, expressing only the Va12.1/Vb5.6 TCR on their surface, showed substantial cytolytic activities to the peptide-loaded target cells which express HLA-B*3501, -B*5101, -B*5301, or -B*0702 molecules, providing the evidence that a single TCR complex has an ability to recognize the same peptide presented by a broad range of HLA molecules. These findings indicate the additional level of crossreactivity of T cells, demonstrating that a certain TCR complex predominantly interacts with the peptide antigen and that an HLA molecule acts like solely a scaffolding component for the peptide rather than the restriction element for the TCR. In addition, a TCR exhibiting a flexible interaction with multiple HLA molecules in complexed with the same peptide would provide further insights into the generation of allorestricted, peptide-specific T cells that are of interest for clinical applications.
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