Antonio Lanzavecchia

Our laboratory investigates the two antigen receptors of human adaptive immunity — immunoglobulins and T cell receptors — and how they can be discovered and engineered to confer protection against infectious diseases and cancer. Using high-throughput cellular screens of human memory B cells and plasma cells, we have isolated potent and broadly neutralizing antibodies for the prophylaxis and treatment of infectious diseases, with a current focus on flaviviruses. In parallel, we continue to address fundamental aspects of the antibody response, such as the role of somatic mutations in affinity maturation, the relationship between infection and autoimmunity, and the diversification of antibodies through templated insertions of genomic DNA into antibody genes. We are now extending the same discovery and engineering logic from antibodies to T cell receptors. Combining immunopeptidomic mapping of naturally presented peptides, antigen-presenting cells engineered to display defined antigens or peptide–HLA complexes, and stringent in vitro selection that enriches for the highest-avidity receptors, we have built a pipeline to isolate self- or allo-restricted T cell receptors against widely presented tumour- and tissue-specific self-antigens for adoptive cell therapy. We also investigate fundamental aspects of the T cell response, including the rules of immunodominance and the specificity of regulatory T cells.