Speaker
Description
In response to infection or vaccination, our immune system creates antibodies that bind strongly to relevant antigens through an evolutionary process called affinity maturation, which involves rounds of somatic hypermutation and selection. A key aspect of this process is the binding affinity landscape, which describes the mapping between antibody sequence and binding affinity to various antigens, and hence plays a role roughly analogous to the fitness landscape (though there are also many other important factors involved). I will describe a combinatorial library assembly and yeast-display system we have developed to systematically measure combinatorially complete binding affinity landscapes relevant for the maturation of broadly neutralizing anti-influenza antibodies (bnAbs). Our results show how widespread epistasis (including high-order epistasis) and pleiotropy may constrain the evolution of these bnAbs.
