HLA-E-restricted, Gag-specific CD8+ T cells can suppress HIV-1 infection, offering vaccine opportunities

Hongbing Yang; Margarida Rei; Simon Brackenridge; Elena Brenna; Hong Sun; Shaheed Abdulhaqq; Michael K P Liu; Weiwei Ma; Prathiba Kurupati; Xiaoning Xu; Vincenzo Cerundolo; Edward Jenkins; Simon J Davis; Jonah B Sacha; Klaus Früh; Louis J Picker; Persephone Borrow; Geraldine M Gillespie; Andrew J McMichael

doi:10.1126/sciimmunol.abg1703

HLA-E-restricted, Gag-specific CD8⁺ T cells can suppress HIV-1 infection, offering vaccine opportunities

Sci Immunol. 2021 Mar 25;6(57):eabg1703. doi: 10.1126/sciimmunol.abg1703.

Authors

Hongbing Yang¹, Margarida Rei², Simon Brackenridge¹, Elena Brenna¹, Hong Sun^{1

3

4}, Shaheed Abdulhaqq⁵, Michael K P Liu⁶, Weiwei Ma⁶, Prathiba Kurupati², Xiaoning Xu⁶, Vincenzo Cerundolo², Edward Jenkins², Simon J Davis², Jonah B Sacha⁵, Klaus Früh⁵, Louis J Picker⁵, Persephone Borrow¹, Geraldine M Gillespie¹, Andrew J McMichael⁷

Affiliations

¹ NDM Research Building, Nuffield Department of Medicine, Oxford University, Oxford OX3 7FZ, UK.
² MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, Oxford University, Oxford OX3 9DS, UK.
³ Key Laboratory of AIDS Immunology, Department of Laboratory Medicine, First Affiliated Hospital of China Medical University, Shenyang, China.
⁴ Chinese Academy of Medical Sciences Oxford Institute, NDM, Oxford University, Oxford, UK.
⁵ Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR 97006, USA.
⁶ Centre For Immunology and Vaccinology, Chelsea and Westminster Hospital, Imperial College, London, UK.
⁷ NDM Research Building, Nuffield Department of Medicine, Oxford University, Oxford OX3 7FZ, UK. andrew.mcmichael@ndm.ox.ac.uk.

Abstract

Human leukocyte antigen-E (HLA-E) normally presents an HLA class Ia signal peptide to the NKG2A/C-CD94 regulatory receptors on natural killer (NK) cells and T cell subsets. Rhesus macaques immunized with a cytomegalovirus-vectored simian immunodeficiency virus (SIV) vaccine generated Mamu-E (HLA-E homolog)-restricted T cell responses that mediated post-challenge SIV replication arrest in >50% of animals. However, HIV-1-specific, HLA-E-restricted T cells have not been observed in HIV-1-infected individuals. Here, HLA-E-restricted, HIV-1-specific CD8 ⁺ T cells were primed in vitro. These T cell clones and allogeneic CD8 ⁺ T cells transduced with their T cell receptors suppressed HIV-1 replication in CD4 ⁺ T cells in vitro. Vaccine induction of efficacious HLA-E-restricted HIV-1-specific T cells should therefore be possible.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Biomarkers
CD8-Positive T-Lymphocytes / immunology*
CD8-Positive T-Lymphocytes / metabolism
Cell Line, Tumor
Cytokines / metabolism
Epitopes, T-Lymphocyte / chemistry
Epitopes, T-Lymphocyte / immunology
HIV Infections / immunology*
HIV Infections / metabolism
HIV Infections / prevention & control
HIV Infections / virology
HIV-1 / immunology*
HLA-E Antigens
Histocompatibility Antigens Class I / immunology*
Host-Pathogen Interactions / immunology*
Humans
Immunophenotyping
Jurkat Cells
Lymphocyte Activation / genetics
Lymphocyte Activation / immunology
Peptides / chemistry
Peptides / immunology
Receptors, Antigen, T-Cell / chemistry
Receptors, Antigen, T-Cell / genetics
Receptors, Antigen, T-Cell / metabolism
T-Cell Antigen Receptor Specificity / immunology
gag Gene Products, Human Immunodeficiency Virus / immunology*

Substances

Biomarkers
Cytokines
Epitopes, T-Lymphocyte
Histocompatibility Antigens Class I
Peptides
Receptors, Antigen, T-Cell
gag Gene Products, Human Immunodeficiency Virus

Abstract

Publication types

MeSH terms

Substances

Grants and funding