The function of MHC class II molecules is to bind peptides derived from antigens that access the endocytic route of antigen presenting cells and display them on the plasma membrane for recognition by CD4(+) T cells. Formation of the MHC II-peptide complexes entails the confluence of the antigens and the MHC II molecules in the same compartments of the endocytic route. There, both the antigens and the MHC II molecules undergo a series of orchestrated changes that involve proteases, other hydrolases and chaperones, culminating in the generation of a wide repertoire of MHC II-peptide combinations. All the events that lead to formation of MHC II-peptide complexes show a considerable degree of flexibility; this lack of strict rules is advantageous in that it provides T cells with the maximum amount of information, ensuring that pathogens do not go undetected.