Model of mechanisms that may contribute to lack of protection by antiviral CD8 T cells in HIV infection.

(1) HIV-1–infected cells are not recognized because of viral escape mutations or nef-mediated down-modulation of class I molecules, (2) signaling is impaired because of CD3ζ and CD28 down-modulation, (3) cytotoxicity is inhibited by expression of NK inhibitory receptors (KIR), (4) cytotoxicity is ineffective because of lack of PFP in cytotoxic granules, and (5) antigen-specific CTLs do not efficiently reach sites of infection because of down-modulation of homing receptors. Figure modified from Chen et al.107