The evolutionary emergence of adaptive immunity has significantly extended the lifespan of humans and other species. The adaptive immune system is essential for host survival and adaptation to the rapidly changing environment, however, it also leads to self-antigen recognition that creates the risk of autoimmune disease. However, it is difficult to trace back to the initial causative event of pathogen infection that occurs long before the clinical onset of autoimmune disease. The recognitions of foreign-and self-antigens are faithfully registered by the individual’s immune repertoire. In this study, through interrogating 1414 T-cell repertoires collected during the COVID-19 pandemic, we sought to trace the immunological host defense against COVID-19 infection, while investigating whether such disturbance of T-cell repertoire will lead to auto-reactive T cells. The percentages of ankylosing spondylitis (AS)-specific T cells were significantly increased with increasing COVID-19-specific T cells (p < 0.0001, rho = 0.38; Fig. 1B). This finding implies a plausible trade-off between the benefit of host survival and the risk of chronic diseases, most of which largely do not affect host reproduction. As such, given that the immunological host defense serves as the top priority of host survival, the adaptive immune system may work at the expense of health risk. This finding has important implications for the primary prevention of autoimmune disease and the vaccine design strategy for COVID-19. Moreover, this study provides a feasible workflow to profile the probability of TCR-antigen cross-reactivity.
Copyright © 2023. Published by Elsevier B.V.