KINETIC ANALYSIS OF ANTIGEN-PRESENTATION OF HIV-INFECTED CELLS USING SOLUBLE T CELL RECEPTORS

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A dual specific human CTL clone harboring one β and two in-frame α transcripts of T cell receptor (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 present study, a retrovirus-mediated TCR transfer of individual α and β chains to TCR-negative hybridoma showed that Vα12.1 TCR in complex with Vβ5.6 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-α chain was not somehow expressed on the cell surface. Remarkably, the Vα12/Vβ5.6 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 Vα12/Vβ5.6 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 Vα12/Vβ5.6 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 antigen 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.