The intracellular assembly of antigenic-peptide-class II complexes

The immune system employs remarkable strategies to ensure that foreign antigens, from the most complex pathogens to the simplest proteins, are displayed on the surfaces of cells which are targets of T lymphocyte recognition. At the heart of these strategies is the molecular transformation of a soluble protein antigen to a complex of a small peptide containing the antigenic determinant bound to a cell surface Major Histocompatibility Complex class I or class II protein. This process is termed antigen presentation. Progress in a variety of laboratories over the last several years has yielded a wealth of information about the molecular mechanisms underlying antigen presentation, providing potential new approaches to vaccine design. Here we describe recent studies in our laboratory aimed at elucidating the intracellular site in B lymphocytes in which antigenic peptide-class II complexes are assembled for recognition by helper T cells and the regulation of this assembly process. Our results suggest that processed antigen-class II complexes are assembled in a unique compartment in the endocytic route which contains all the necessary cellular and molecular machinery for assembly and that B cells regulate the assembly process in response to external and internal signals.