Antigenic peptides are presented to T cells from two sources: proteins generated inside the cell (as in the case of virally infected cells or tumor cells) or from an extracellular pool. In the latter situation, class II major histocompatibility complex (MHC) molecules on antigen-presenting cells (APCs) present peptide fragments to CD4+ helper T cells, whereas MHC class I molecules display peptides to CD8+ T cells in a process known as cross-presentation. Burgdorf et al. reveal that the two pathways for presenting peptides from the same extracellular antigen are determined by the mode of antigen uptake by the APCs. For class I restricted presentation, surface mannose receptors (MRs) routed antigen to the stable early endosome compartment where peptides could meet MHC class I molecules. In contrast, pinocytosis of the same antigen directed it to the lyosomal compartment for presentation by class II MHC. The findings will help resolve questions about how APCs activate and modulate different arms of the T cell response.
S. Burgdorf, A. Kautz, V. Böhnert, P. A. Knolle, C. Kurts, Distinct pathways of antigen uptake and intracellular routing in CD4 and CD8 T cell activation. Science 316, 612-616 (2007). [Abstract] [Full Text]