B-cell co-receptors: The two-headed antigen

The immune response is initiated when an antigen is recognized by specific lymphocytes. Originally, ‘antigen’ was viewed as a simple entity that bound directly to lymphocyte antigen receptors: the B-cell antigen receptor complex that includes membrane-bound immunoglobulin, or the T-cell antigen receptor. It has been clear for a number of years, however, that conventional T cells recognize not free antigen, but rather antigen-derived peptides bound to proteins of the major histocompatibility complex (MHC). Now it is becoming clear that the antigen interacting with B cells may similarly interact with other molecules of the immune system that allow the B cell to gain additional information, affecting its response. In both T cells and B cells, the complexed antigen can bind not only the antigen receptor, but also a second cellsurface receptor referred to as the co-receptor. The complexed antigen brings together the antigen receptor and the co-receptor, with the result that antigen-receptor signaling events are altered and the cell responds accordingly. This principle has now been used to create antigens for B cells that are extremely good at stimulating the cells to generate an antibody response [1].