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

使用可溶性 T 细胞受体对 HIV 感染细胞的抗原呈递进行动力学分析

基本信息

批准号：
13670300
负责人：
UENO Takamasa
金额：
$ 2.3万
依托单位：
KUMAMOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670300/
关键词：
T CELL RECEPTOR ANTIGEN PRESENTATION HLA CYTOTOXIC T LYMPHOCYTE HIV CELLULAR IMMUNITY RECOMBINANT PROTEIN SURFACE PLASMON RESONANCE 細胞傷害性T細胞組換え蛋白質

项目摘要

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.

先前据报道，携带一个β的双重特异性克隆和两个T-Cell受体（TCR）的转录本被报道，在目前，由Syngeneic HLA-B*3501和HLA-b*5101 tort骨衍生的非肽（iplteeeael）研究，逆转录病毒介导的TCR转移α和β-TCR阴性杂交瘤表明，MPLEX中的Vα12.1TCR具有Vβ5.6，在HLA-B*3501和HLA-B*5101，均导致了Peppecific响应。确认单个TCRE TCRE双重特殊性。当肽通过合同性和同种异体HLA II类分子eover提出肽时，/vβ5.6TCR似乎是可比的，CTL克隆携带Vα2/Vβ5.6TCR表现出对表达HLA-B *35011111350111的肽的细胞的实质性细胞溶解活性，HLA-B*5101，HLA-B*5301或HLA-B*0702，进一步提供单个TCREX可以通过一系列HLA I类分子识别同一肽。 HLA Moltiple可能会为产生异肌特异性T细胞的产生提供优势，因此可以成为抗HIV感染的免疫疗法的有效候选者。