Dendritic Cross-Presentation Modulates Immune Response

In a new study, researchers describe the mechanics of a pathway in dendritic cells responsible for the crosspresentation of antigens to T-cells when the immune system responds to invasion by pathogens.

When activated, CD8+ T cells become cytotoxic T lymphocytes (CTLs) and are responsible for eliminating virus-infected cells. CTLs are able to recognize these cells because they display antigens on the cell surface as fragments of viral proteins (peptides) bound to major histocompatibility complex (MHC) class I molecules. Because of their aggressive nature and the risk of inflicting severe autoimmune diseases, the initial activation of CD8+ T-cells must be tightly controlled.

Therefore, while activated CTLs can recognize and kill any type of cell expressing the appropriate antigen, the activation of naive CD8+ T-cells requires the antigen to be initially presented by a specialized subset of bone marrow derived cells known as professional antigen presenting cells (pAPC). These cells are very mobile and can carry antigen from the peripheral tissues into the secondary lymphoid organs where naive CTLs reside. Importantly, pAPC do not necessarily need to be infected because they have a unique capacity to acquire antigen from other infected cells (antigen donor cells, ADC) in the process of crosspresentation.

The investigators, from the University of British Columbia (Vancouver, Canada), detected the existence of an endolysosomal compartment in dendritic cells where exogenously derived peptides could be acquired for presentation to T-cells, and showed that the MHC class I cytoplasmic domain contained a tyrosine-based targeting signal required for routing MHC class I molecules through these compartments. These findings were published October 19, 2003, in the online edition of Nature Immunology.

"This discovery opens the door to the immune system control room,” said senior author Dr. Wilfred Jefferies, professor of biotechnology at the University of British Columbia. "We have found a mechanism that appears to act like a dial. It can turn immune system response up or down.”