Processing and presentation of tumor antigens and vaccination strategies

van der Bruggen, Pierre [UCL] Van den Eynde, Benoît [UCL]

Various new aspects of antigen processing have been uncovered through the study of tumor antigens. One of these is the production of antigenic peptides by splicing of two distinct peptide fragments. In one of the two cases reported, the proteasome was found to be responsible for splicing. The presentation of another peptide on major histocompatibility complex class I molecules was found to depend on secretion and reuptake of the parent protein, implying a cross-presentation pathway in melanoma cells. Class II presentation of peptides derived from cytosolic proteins now appears to result from autophagy. Based on increased knowledge on antigen processing and presentation, new vaccination strategies are aimed at improving the targeting of antigens to dendritic cells, promoting cross-priming (for example, using chloroquine), improving peptide binding to class I molecules and targeting antigens to both the class I and the class II pathways.