Immunity & infection
Conventional T cell paradigm dictates CD8+ T cell recognition of peptides in the context of MHC class I. However, a paradigm shifting study demonstrated that the induction of a novel subset of MHC class II-restricted CD8+ T cells was associated with clearance of SIV infection in rhesus macaques, whereas another study recently highlighted the presence of HIV-1-specific class II-restricted CD8+ T cells in a small subset of HIV-1 patients who naturally control infection (virus controllers; VCs). However, the distribution of these atypical CD8+ T cells in different HIV-1 disease states and their direct role in viral control are still unknown. In this study, we assessed the distribution and ability of MHC class II-restricted CD8+ T cells to suppress HIV-1 replication in autologous CD4+ T cells in different HIV-1 patient cohorts (VCs, chronic viremics and healthy donors) using MHC class II tetramer staining and MHC Blocking Viral Inhibition Assay (VIA), respectively. Six of the seven VC patients analyzed had memory Gag-specific MHC class II-restricted CD8+ T cells, with two of these six patients having persistent class II-restricted CD8+ T cells. Class II CD8+ T cell responses were also detected in chronic viremics at lower frequency than in VCs but were absent in healthy donors. The two VCs with persistent Gag-specific MHCII-restricted CD8+ T cells also exhibited MHCII-blockable antiviral activity, confirming the functionality of their CD8+ MHCII-restricted cells. In summary, functional memory class II-restricted Gag-specific CD8+ T cells are present at low frequencies during natural HIV-1 infection.
Duke Human Vaccine Institute and Center for HIV/AIDS Vaccine Immunology Duke University Medical Cent