Antiviral CD8+ T Cells Restricted by Human Leukocyte Antigen Class II Exist during Natural HIV Infection and Exhibit Clonal Expansion

  • Biology
  • Immunology
  • Infectious Disease
  • Sam Kazer
  • Alex K. Shalek
  • Ranasinghe et al.▾
    Ranasinghe, S., Lamothe, P.A., Soghoian, D.Z., Kazer, S.W., Cole, M.B., Shalek, A.K., Yosef, N., Jones, B., Donaghey, F., Nwonu, C., Jani, P., Clayton, G.M., Crawford, F., White, J., Montoya, A., Power, K., Allen, T.A., Streeck, H., Kaufmann, D.E., Picker, L.J., Kappler, J.W., Walker, B.D.
  • Immunity , Volume 45
  • October, 2016
Biology
Immunology
Infectious Disease
Sam Kazer
Alex K. Shalek

Abstract

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.

Antiviral CD8+ T Cells Restricted by Human Leukocyte Antigen Class II Exist during Natural HIV Infection and Exhibit Clonal Expansion