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CD4+ T cell-mediated HLA class II cross-restriction in HIV controllers
- Source :
- Science Immunology, Science Immunology, American Association for the Advancement of Science, 2018, 3 (24), pp.eaat0687. ⟨10.1126/sciimmunol.aat0687⟩, Science Immunology, 2018, 3 (24), pp.eaat0687. ⟨10.1126/sciimmunol.aat0687⟩
- Publication Year :
- 2018
-
Abstract
- International audience; Rare individuals, termed HIV controllers, spontaneously control HIV infection by mounting efficient T cell responses against the virus. Protective CD4+ T cell responses from HIV controllers involve high-affinity public T cell receptors (TCRs) recognizing an immunodominant capsid epitope (Gag293) presented by a remarkably broad array of human leukocyte antigen (HLA) class II molecules. Here, we determine the structures of a prototypical public TCR bound to HLA-DR1, HLA-DR11, and HLA-DR15 molecules presenting the Gag293 epitope. TCR recognition was driven by contacts with the Gag293 epitope, a feature that underpinned the extensive HLA cross-restriction. These high-affinity TCRs promoted mature immunological synapse formation and cytotoxic capacity in both CD4+ and CD8+ T cells. The public TCRs suppressed HIV replication in multiple genetic backgrounds ex vivo, emphasizing the functional advantage conferred by broad HLA class II cross-restriction.
- Subjects :
- 0301 basic medicine
T cell
MESH: HLA-D Antigens
Immunology
Human leukocyte antigen
Biology
Epitope
MESH: Cross Reactions
MESH: HIV-1
MESH: Primary Cell Culture
03 medical and health sciences
0302 clinical medicine
Immune system
[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases
MESH: Jurkat Cells
medicine
Cytotoxic T cell
MESH: Animals
MESH: Healthy Volunteers
MESH: Lymphocyte Activation
[SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology
MESH: Mice
MESH: Humans
Immunological synapse formation
MESH: Virus Replication
MESH: Host-Pathogen Interactions
T-cell receptor
MESH: CD4-Positive T-Lymphocytes
MESH: Receptors, Antigen, T-Cell
MESH: HIV Infections
General Medicine
Virology
3. Good health
MESH: Leukocytes, Mononuclear
[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology
030104 developmental biology
medicine.anatomical_structure
MESH: Fibroblasts
MESH: HEK293 Cells
030220 oncology & carcinogenesis
[SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases
MESH: Viral Load
CD8
Subjects
Details
- Language :
- English
- ISSN :
- 24709468
- Database :
- OpenAIRE
- Journal :
- Science Immunology, Science Immunology, American Association for the Advancement of Science, 2018, 3 (24), pp.eaat0687. ⟨10.1126/sciimmunol.aat0687⟩, Science Immunology, 2018, 3 (24), pp.eaat0687. ⟨10.1126/sciimmunol.aat0687⟩
- Accession number :
- edsair.doi.dedup.....8b1364c6d98ab51af27681c72e4a2ec1