Virus-specific CD4+ T cells: ready for direct attack

Abstract

CD4+ T cells are classically thought to orchestrate adaptive immune responses. But recent studies demonstrate that they can also kill infected cells directly. A new paper shows that highly efficient processing of Epstein Barr virus (EBV) glycoproteins for presentation on MHC class II makes virus-transformed B cells susceptible to lysis by CD4+ T cells. Thus, antiviral vaccines should aim to stimulate both helper and cytolytic CD4+ T cells.

Figure 1.

Exogenous and endogenous MHC class II antigen processing pathways lead to direct recognition of virus-infected cells by CD4⁺ T cells. Uptake of infected cell fragments (1) or virions (4) leads to MHC class II presentation of viral antigens. In addition, viral envelope as well as cytosolic or nuclear antigens reach the MIIC via the secretory pathway from the endoplasmic reticulum (ER) (2) or after macroautophagy of cytoplasm (3), respectively. After transport to the cell surface, the complexes of MHC class II molecules and viral antigen fragments are recognized by CD4⁺ T cells, which then either secrete IFNγ to restrict viral replication or kill the infected cell via FasL and perforin-granzyme–dependent mechanisms.