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

作者: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*
来源:Immunity, 2016, 45(4): 917-930.
DOI:10.1016/j.immuni.2016.09.015

摘要

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 beta (TCR beta) 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 TCR alpha analysis revealed two distinct co-expressed TCRa 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.