biostudies-literatureRanasinghe SQuebec Health Research FundBeckman Young Investigator ProgramSearle Scholars ProgramHoward Hughes Medical InstituteNIAID NIH HHSRagon InstituteHHMI International Student Research FellowshipNIAIDNIHNIH/NIAIDNIH New Innovator AwardNSF Graduate Research FellowshipVir Bio, Inc.NIGMS NIH HHSBill & Melinda Gates Foundation Collaboration for AIDS Vaccine Discovery917-930https://www.ebi.ac.uk/biostudies/studies/S-EPMC5077698biostudies-literatureUnknown45(4)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.ImmunityAntiviral CD8⁺ T Cells Restricted by Human Leukocyte Antigen Class II Exist during Natural HIV Infection and Exhibit Clonal Expansion.PMC5077698U24 AI11862-01P01 AI104715P30 AI060354AI104715U24 AI1186725P30AI060354DP2 GM119419R21 AI125085DP2 OD020839APP1108533Donaghey FWalker BDKaufmann DEWhite JClayton GMPower KCrawford FPicker LJRanasinghe SJani PKazer SWYosef NKappler JWAllen TMShalek AKNwonu CStreeck HSoghoian DZJones RBCole MBMontoya ALamothe PAfalseAntiviral CD8⁺ T Cells Restricted by Human Leukocyte Antigen Class II Exist during Natural HIV Infection and Exhibit Clonal Expansion.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.2016-01-01T00:00:00Z2016 Oct2025-04-04T09:21:53.555Z2019-03-27T02:27:24ZS-EPMC50776982776034210.1016/j.immuni.2016.09.015