Single T cell receptor-mediated recognition of an identical HIV-derived peptide presented by multiple HLA class I molecules.
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 Valpha12.1 TCR in complex with Vbeta5.6 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 Valpha12.1/Vbeta5.6 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 Valpha12/Vbeta5.6 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 Valpha12.1/Vbeta5.6 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.
Ueno
Takamasa
T
Division of Viral Immunology, Center for AIDS Research, Kumamoto University, Japan.
Tomiyama
Hiroko
H
Takiguchi
Masafumi
M
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D002462:Cell Membrane / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D002999:Clone Cells; D003001:Cloning, Molecular; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D015684:Gene Products, pol / Q000276:immunology* / Q000378:metabolism; D019673:Genes, T-Cell Receptor alpha; D019674:Genes, T-Cell Receptor beta; D015497:HIV-1 / Q000276:immunology*; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015235:HLA-B Antigens / Q000276:immunology / Q000378:metabolism; D015797:HLA-B35 Antigen / Q000276:immunology / Q000378:metabolism; D059949:HLA-B51 Antigen; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D006825:Hybridomas; D051379:Mice; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000276:immunology* / Q000378:metabolism; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014161:Transduction, Genetic
D015684:Gene Products, pol; D006680:HLA Antigens; D015235:HLA-B Antigens; D015797:HLA-B35 Antigen; D059949:HLA-B51 Antigen; D015395:Histocompatibility Antigens Class I; D009842:Oligopeptides; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta