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

免疫系统的T细胞对抗原的识别是脊椎动物中病原体特异性免疫应答的中心过程。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。这种变异性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未完全了解。在这个项目中，我们从进化的角度研究了三棘鱼（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。采用新的分子技术和测序技术，我们能够研究个体刺鱼之间T细胞库的变异性以及从出生到生命结束的发展。具体来说，我们在这里调查的动态响应的T细胞库暴露与个别抗原，以及全方位的自然寄生虫社区，棘鱼暴露在其自然栖息地。此外，我们研究了T细胞库的可变性与棘鱼的微生物组之间的关系，这被怀疑是调节T细胞驱动的免疫力。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。

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.