CD8(+) T cell recognition of virus-infected cells is characteristically restricted by major histocompatibility complex (MHC) class I, although rare examples of MHC class II restriction have been reported in Cd4-deficient mice and a macaque SIV vaccine trial using a recombinant cytomegalovirus vector. Here, we demonstrate the presence of human leukocyte antigen (HLA) class II-restricted CD8(+) T cell responses with antiviral properties in a small subset of HIV-infected individuals. In these individuals, T cell receptor β (TCRβ) analysis revealed that class II-restricted CD8(+) T cells underwent clonal expansion and mediated killing of HIV-infected cells. In one case, these cells comprised 12% of circulating CD8(+) T cells, and TCRα analysis revealed two distinct co-expressed TCRα chains, with only one contributing to binding of the class II HLA-peptide complex. These data indicate that class II-restricted CD8(+) T cell responses can exist in a chronic human viral infection, and may contribute to immune control.
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Ranasinghe, S., Lamothe, P., Soghoian, D., Kazer, S., Cole, M., Shalek, A., Yosef, N., Jones, R. B., Donaghey, F., Nwonu, C., Jani, P., Clayton, G., Crawford, F., White, J., Montoya, A., Power, K., Allen, T., Streeck, H., Kaufmann, D., Picker, L., Kappler, J., & Walker, B. (2016). Antiviral CD8(+) T Cells Restricted by Human Leukocyte Antigen Class II Exist during Natural HIV Infection and Exhibit Clonal Expansion.. Immunity, 45 (4). http://dx.doi.org/10.1016/j.immuni.2016.09.015