Unusual antigen presentation offers new insight into HIV vaccine design

- A rhesus cytomegalovirus (RhCMV) CMV vaccine generates MHC-E restricted CD8+ T cell responses.
- MHC-E normally binds a signal peptide from classical MHC-I molecules.
- MHC-E presentation of other peptides to CD8+ T ​cells involves alternate antigen processing pathways.
- CMV genes have a role in changing antigen processing.

Recent findings with a rhesus monkey cytomegalovirus based simian immunodeficiency virus vaccine have identified strong CD8+ T cell responses that are restricted by MHC-E. Also mycobacteria specific CD8+ T cells, that are MHC-E restricted, have been identified. MHC-E therefore can present a wide range of epitope peptides to CD8+ T cells, alongside its well defined role in presenting a conserved MHC-class I signal peptide to the NKG2A/C-CD94 receptor on natural killer cells. Here we explore the antigen processing pathways involved in these atypical T cell responses.