MHC-I-restricted presentation of HIV-1 virion antigens without viral replication

Dendritic cells and macrophages can process extracellular antigens for pres entation by MHC-I molecules. This exogenous pathway may have a crucial role in the activation of CD8(+) cytotoxic T lymphocytes during human viral inf ections. We show here that HIV-1 epitopes derived from incoming virions are presented through the exogenous MHC-I pathway in primary human dendritic c ells, and to a lower extent in macrophages, leading to cytotoxic T-lymphocy te activation in the absence of viral protein synthesis. Exogenous antigen presentation required adequate virus-receptor interactions and fusion of vi ral and cellular membranes. These results provide new insights into how ant i-HIV cytotoxic T lymphocytes can be activated and have implications for an ti-HIV vaccine design.