The role of T cell receptor avidity in determining T cell repertoires and responses

T 细胞受体亲合力在确定 T 细胞库和反应中的作用

• 批准号: nhmrc : 350395
• 负责人: Prof Nicole La Gruta
• 金额: $ 31.51万
• 依托单位: The University of Melbourne
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2005
• 资助国家: 澳大利亚
• 起止时间: 2005-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/role-t-cell-repertoires-responses/77435
• 关键词: role; cell; receptor; avidity; determining

T cells are an essential component of the immune system. CD8 T cells, in particular, play a vital role in the immune response to viruses and tumors, predominantly via killing of virally infected cells and tumor cells, as well as the release of inflammatory mediators. T cells must be activated before they can mediate such anti-viral or anti-tumor effects and this activation occurs through the binding of pathogen or tumor fragments (peptides) by a receptor on the surface of T cells (T cell receptor). Each individual has an entire repertoire of T cells with unique T cell receptors which interact with peptides with varying binding strengths. After stimulation of T cells by e.g. viral infection, a subset of the T cell repertoire will become expanded and dominate the anti-viral immune response. This study aims to investigate how, during a viral infection, the strength (or 'avidity') of the interaction between the T cell receptor and the peptide influences (i) whether or not a T cell clone is recruited into the immune response and, if so, its dominance over other clones within that response, and (ii) how efficiently a T cell is activated. It is anticipated that particular virus peptide-specific T cell populations with an overall high avidity will be better able to produce inflammatory mediators and kill infected cells compared to lower avidity T cell populations specific for a different virus peptide. It is also expected that the higher avidity populations will exhibit greater diversity of TCRs. Further, within peptide-specific populations, it is anticipated that the relatively high avidity T cell clones will dominate the specific response. This study will contribute to a greater understanding of factors contributing to T cell recruitment and activation. Armed with this knowledge we will be better able to design vaccines to elicit optimal T cell responses to viral infection.

T细胞是免疫系统的重要组成部分。特别是CD8 T细胞，在对病毒和肿瘤的免疫应答中起着至关重要的作用，主要是通过杀死病毒感染的细胞和肿瘤细胞，以及释放炎症介质。T细胞必须在它们可以介导这种抗病毒或抗肿瘤作用之前被激活，并且这种激活通过T细胞表面上的受体（T细胞受体）结合病原体或肿瘤片段（肽）而发生。每个人都有一个完整的T细胞库，具有独特的T细胞受体，与不同结合强度的肽相互作用。在通过例如病毒感染刺激T细胞后，T细胞库的子集将扩增并主导抗病毒免疫应答。本研究旨在研究在病毒感染期间，T细胞受体和肽之间相互作用的强度（或“亲合力”）如何影响（i）T细胞克隆是否被招募到免疫应答中，如果是，则其在该应答中对其他克隆的优势，以及（ii）T细胞激活的效率。预期具有总体高亲合力的特定病毒肽特异性T细胞群体与对不同病毒肽特异性的较低亲合力T细胞群体相比将能够更好地产生炎性介质并杀死感染的细胞。还预期较高亲合力的群体将表现出更大的TCR多样性。此外，在肽特异性群体中，预期相对高亲合力的T细胞克隆将主导特异性应答。这项研究将有助于更好地了解T细胞募集和激活的因素。有了这些知识，我们将能够更好地设计疫苗，以引发对病毒感染的最佳T细胞反应。