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The Journal of Immunology, 2002, 169: 4961-4969.
Copyright © 2002 by The American Association of Immunologists

Single T Cell Receptor-Mediated Recognition of an Identical HIV-Derived Peptide Presented by Multiple HLA Class I Molecules1

Takamasa Ueno, Hiroko Tomiyama and Masafumi Takiguchi2

Division of Viral Immunology, Center for AIDS Research, Kumamoto University, Kumamoto, Japan

A dual specific human CTL clone harboring one {beta} and two inframe {alpha} transcripts of TCR was previously reported to recognize an HIV Pol-derived nonapeptide (IPLTEEAEL) endogenously presented by both syngeneic HLA-B*3501 and HLA-B*5101. In the current study, a retrovirus-mediated TCR transfer of individual {alpha}- and {beta}-chains to TCR-negative hybridoma showed that V{alpha}12.1 TCR in complex with V{beta}5.6 were responsible for the peptide-specific response in the context of both HLA-B*3501 and HLA-B*5101, confirming single TCR-mediated dual specificity. The second TCR-{alpha} chain was not somehow expressed on the cell surface. Remarkably, the V{alpha}12.1/V{beta}5.6 TCR also recognized the same peptide presented by allogeneic HLA class I molecules that share the similar peptide-binding motifs, such as HLA-B*5301 and HLA-B*0702. The sensitivity of peptide recognition by the V{alpha}12/V{beta}5.6 TCR appeared to be comparable when the peptide was presented by syngeneic and allogeneic HLA class I molecules, with changes in T cell responsiveness caused largely by peptide-binding capacity. Moreover, the CTL clone bearing V{alpha}12.1/V{beta}5.6 TCR showed substantial cytolytic activity against the peptide-loaded cells expressing HLA-B*3501, HLA-B*5101, HLA-B*5301, or HLA-B*0702, providing further evidence that a single TCR complex can recognize the same peptide presented by a broad range of HLA class I molecules. A TCR with fine specificity for an HIV Ag but broad specificity to multiple HLA molecules may provide an advantage to the generation of allorestricted, peptide-specific T cells, and thus could be a potent candidate for immunotherapy against HIV infection.




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