The two main proteolytic machineries of eukaryotic cells, lysosomes and proteasomes, receive substrates by different routes. Polyubiquitination targets proteins for proteasomal degradation, whereas autophagy delivers intracellular material for lysosomal hydrolysis. The importance of autophagy for cell survival has long been appreciated, but more recently, its essential role in both innate and adaptive immunity has been characterized. Autophagy is now recognized to restrict viral infections and replication of intracellular bacteria and parasites. Additionally, this pathway delivers cytoplasmic antigens for MHC class II presentation to the adaptive immune system, which then in turn is able to regulate autophagy. At the same time, autophagy plays a role in the survival and the cell death of T cells. Thus, the immune system utilizes autophagic degradation of cytoplasmic material, to both restrict intracellular pathogens and regulate adaptive immunity.

The gamma-herpesvirus, EBV, is reliably found in a latent state in endemic Burkitt's lymphoma. A single EBV gene product, Epstein-Barr nuclear Ag I (EBNA1), is expressed at the protein level. Several mechanisms prevent immune recognition of these tumor cells, including a block in EBNA1 presentation to CD8(+) killer T cells. Therefore, no EBV-specific immune response has yet been found to target Burkitt's lymphoma. We now find that EBNA1-specific, Th1 CD4(+) cytotoxic T cells recognize Burkitt's lymphoma lines. CD4+ T cell epitopes of EBNA1 are predominantly found in the C-terminal, episome-binding domain of EBNA 1, and similar to0.5% of peripheral blood CD4(+) T cells are specific for EBNA1. Therefore, adaptive immunity can be directed against Burkitt's lymphoma, and perhaps this role for CD4(+) Th1 cells extends to other tumors that escape MHC class I presentation.