HIV-1-Infected CD4⁺ T Cells Present MHC Class II-Restricted Epitope via Endogenous Processing

HIV-1-specific CD4⁺ T cells (T_CD4+s) play a critical role in controlling HIV-1 infection. Canonically, T_CD4+s are activated by peptides derived from extracellular ("exogenous") Ags displayed in complex with MHC class II (MHC II) molecules on the surfaces of "professional" APCs such as dendritic cells (DCs). In contrast, activated human T_CD4+s, which express MHC II, are not typically considered for their APC potential because of their low endocytic capacity and the exogenous Ag systems historically used for assessment. Using primary T_CD4+s and monocyte-derived DCs from healthy donors, we show that activated human T_CD4+s are highly effective at MHC II-restricted presentation of an immunodominant HIV-1-derived epitope postinfection and subsequent noncanonical processing and presentation of endogenously produced Ag. Our results indicate that, in addition to marshalling HIV-1-specific immune responses during infection, T_CD4+s also act as APCs, leading to the activation of HIV-1-specific T_CD4+s.