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

• Published in: Immunity (Cambridge, Mass.) Mass.), 2016-10, Vol.45 (4), p.917-930
• Main Authors: Ranasinghe, Srinika, Lamothe, Pedro A., Soghoian, Damien Z., Kazer, Samuel W., Cole, Michael B., Shalek, Alex K., Yosef, Nir, Jones, R. Brad, Donaghey, Faith, Nwonu, Chioma, Jani, Priya, Clayton, Gina M., Crawford, Frances, White, Janice, Montoya, Alana, Power, Karen, Allen, Todd M., Streeck, Hendrik, Kaufmann, Daniel E., Picker, Louis J., Kappler, John W., Walker, Bruce D.
• Format: Article
• Language: English
• Subjects: Acquired immune deficiency syndrome; AIDS; Amino acids; Antigens; Antiviral Agents - immunology; CD8+ T cells; CD8-Positive T-Lymphocytes - immunology; Cytomegalovirus; Expansion; Herpesviridae; Histocompatibility Antigens Class II - immunology; HIV; HIV Infections - immunology; HLA; HLA Antigens - immunology; Human immunodeficiency virus; Humans; Infections; Lentivirus; Lymphocytes; Macaca; MHC class II; Peptides; Receptors, Antigen, T-Cell, alpha-beta - immunology; Retroviridae; Scholarships & fellowships; Statistical analysis; T cell receptors; TCR; Vaccines; Viral infections; Viruses
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2016.09.015

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. •CD8+ T cells restricted by HLA-DRB1 exist in a small number of HIV-infected persons•These CD8+ T cells exhibit potent antiviral functions against HIV-infected cells•TCRβ usage patterns indicate clonal expansion of class II-restricted CD8+ T cells•CD8+ T cells that violate immunologic paradigms may contribute to viral control MHC class II-restricted CD8+ T cells have been reported in Cd4-deficient mice and an SIV vaccine trial. Ranasinghe et al. demonstrate that HLA class II-restricted CD8+ T cells also exist in a small percentage of HIV-infected individuals, show potent antiviral functions against HIV-infected cells, and exhibit atypical TCR usage patterns.