|2023/2024||Victor Greiff||Associate Professor||Univeristy of Oslo (UiO)|
The adaptive immune response operates via so-called adaptive immune receptors (AIRs, comprise antibodies and T-cell receptors), of which there are about 108–1010 different ones in each human individual. AIRs are fundamentally important in fighting disease and infection. AIRs can recognize nearly any invading pathogen. Yet, counter to current simplified textbook illustrations, the adaptive immune response to recognizing evolutionarily new (that means, only recently encountered antigens by humans) pathogens is poor. This is exemplified by the disease-driven decimation of South Americans after the Spanish invasion (1500 and 1600s) or the generally poor immune response to HIV.
In contrast, pathogens that humans have continuously interacted with, such as influenza, are generally handled well or at least better by the immune system. Therefore, it has been hypothesized that historical environmental antigen exposures have imprinted on adaptive immunity over evolutionary time, rendering our immune system more adept at recognizing those pathogens our ancestors have repeatedly encountered in the past. Indeed, there has been a renewed recent interest in evolutionary immunology, specifically in high-profile journals (1, 2). However, these works focused on innate immunity and not the malleable, adaptive immunity hindering an evolutionary, and therefore, causal and fundamental understanding of the variation in the quality of the adaptive immune response to different pathogens. The objective and research question of this EVOIMMPRINT project is to achieve a comprehensive overview of the evidence of evolutionary imprints on adaptive immunity. Towards this objective, we will create a network of researchers with world-leading expertise in immunology, structural and evolutionary biology, and machine learning. EVOIMMPRINT has fundamental and ground-breaking implications for the understanding, prediction, and engineering of adaptive immunity.