T cells can be categorized according to their expression of the glycoproteins CD4 or CD8 on their cell surface. CD8+ T cells recognize peptides presented by major histocompatibility complex class I (MHCI), whereas CD4+ T cells recognize peptides in the context of MHCII. A new study suggests that this distinction is not absolute by showing that that a simian immunodeficiency virus (SIV) vaccine can elicit SIV-specific CD8+ T cells that recognize MHCII-restricted epitopes (Science 340, 1237874).

Louis Picker and his colleagues had previously reported a potential HIV vaccine strategy that used a recombinant rhesus macaque cytomegalovirus (CMV) vector to express SIV proteins (RhCMV/SIV), which yielded impressive levels of protection in vaccinated rhesus macaques. They noticed, however, that the RhCMV/SIV vectors did not induce canonical CD8+ T cell responses, which the virus is known to escape. In their new work, the authors investigated the nature of the CD8+ T cell responses induced by this vaccine in more depth. They found that the recombinant RhCMV/SIV (strain 68-1 RhCMV/SIV) elicited CD8+ T cell responses that are distinct from those induced by SIV or by a wild-type RhCMV vector expressing SIV proteins. Whereas CD8+ T cells induced by a virus usually focus on only a small number of epitopes, strain 68-1 RhCMV/SIV could elicit more promiscuous CD8+ T cell responses to a broad range of SIV epitopes and, notably, to those presented by both MHCI and MHCII.

The authors then compared the CD8+ T cell responses induced by strain 68-1 RhCMV/SIV with RhCMV vectors bearing different CMV deletions, allowing them to identify rhesus CMV genes that regulate these responses. As these key CMV genes have human CMV homologs, it may be possible to design vectors that can induce similarly broad T cell responses in humans against HIV and other viruses. Further studies will also be required to dissect the mechanisms by which RhCMV vectors elicit these paradigm-violating T cell responses and to determine whether such T cell responses can be manipulated to create an effective HIV vaccine.