T cell receptor diversity and T cell repertoire dynamics in an eco-evolutionary model species

生态进化模型物种中 T 细胞受体多样性和 T 细胞库动态

• 批准号: 433116033
• 负责人: Professor Dr. Tobias Lenz
• 金额: --
• 依托单位: Institut für Zell- und Systembiologie der Tiere (IZS)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/433116033?language=en
• 关键词: cell; receptor; diversity; repertoire; dynamics

The recognition of antigens by T cells of the immune system is a central process of a pathogen-specific immune response in vertebrates. The ability of the adaptive immune system to continuously recognize novel antigens is based on a complex interaction of higly variable molecules in the body. The genetic basis for this variability has presumably evolved through the continuous interaction with diverse pathogens, but the exact factors and mechanism behind this evolutionary process are not yet fully understood. In this project, we examine the T-cell repertoire of the three-spined stickleback (Gasterosteus aculeatus) from an evolutionary perspective. The stickleback has become a model species for studying complex evolutionary processes, including the coevolution between hosts and their parasites. In principle, the stickleback’s immune system functions in the same way as the one in humans, so that the findings from our research can also provide insights into the evolution and complexity of the human immune system. Employing novel molecular techniques and sequencing technologies, we are able to study the variability of the T cell repertoire among individual sticklebacks as well as its development from birth to the end of life. Specifically, we investigate here the dynamic response of the T-cell repertoire to exposure with individual antigens, as well as the the full range of the natural parasite community that the stickleback is exposed to in its natural habitat. Furthermore, we investigate the relationship between the variability of the T cell repertoire and the microbiome of the stickleback, which is suspected to modulate T cell-driven immunity. The results of this project will provide new insights into the evolution of the T cell-based adaptive immune system, and ultimately lead to a better understanding of the genetic basis of differences in immune competence among individuals.

免疫系统的T细胞对抗原的识别是脊椎动物病原体特异性免疫反应的中心过程。适应性免疫系统持续识别新抗原的能力是基于体内高度可变分子的复杂相互作用。这种变异的遗传基础可能是通过与不同病原体的持续相互作用而进化的，但这一进化过程背后的确切因素和机制尚不完全清楚。在这个项目中，我们从进化的角度研究了三棘棘鱼（Gasterosteus aculeatus）的t细胞库。棘鱼已经成为研究复杂进化过程的模式物种，包括宿主和寄生虫之间的共同进化。原则上，棘鱼的免疫系统与人类的免疫系统功能相同，因此我们的研究结果也可以为人类免疫系统的进化和复杂性提供见解。利用新的分子技术和测序技术，我们能够研究单个刺鱼之间T细胞库的变异性以及它从出生到生命结束的发育过程。具体来说，我们在这里研究了t细胞库对暴露于单个抗原的动态反应，以及刺鱼在其自然栖息地暴露于天然寄生虫群落的全范围。此外，我们研究了T细胞库的可变性和棘鱼微生物组之间的关系，这被怀疑是调节T细胞驱动的免疫。该项目的结果将为基于T细胞的适应性免疫系统的进化提供新的见解，并最终导致更好地理解个体之间免疫能力差异的遗传基础。