Immunity. 2016 Oct 18; 45(4):917-930.

PubMed ID: 27760342

Antiviral CD8+; T cells restricted by human leukocyte antigen class II exist during natural HIV infection and exhibit clonal expansion

Ranasinghe S, Lamothe PA, Soghoian DZ, Kazer SW, Cole MB, Shalek AK, Yosef N, Jones RB, Donaghey F, Nwonu C, Jani P, Clayton GM, Crawford F, White J, Montoya A, Power K, Allen TM, Streeck H, Kaufmann DE, Picker LJ, Kappler JW, Walker BD

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.