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Stimulation of HIV-specific T cell clonotypes using allogeneic HLA
Coral-Ann Almeida1, Paula van Miert2, Kane O'Driscoll3
1Department of Clinical Immunology, Fiona Stanley Hospital, Perth, Australia; Pathwest Laboratory Medicine, Perth, Australia; Pathology and Laboratory Medicine, University of Western Australia, Perth, Australia.
Cellular Immunology
|April 5, 2017
Summary
HIV-specific CD8 T cells can recognize and respond to foreign HLA molecules. This allorecognition, specific to the HIV target and T cell receptor, suggests a new strategy for boosting HIV immunity.
Area of Science:
- Immunology
- Virology
- Genetics
Background:
- Human Immunodeficiency Virus (HIV) infection establishes chronic immune activation.
- CD8 T cells are crucial for controlling viral infections, including HIV.
- Understanding T cell recognition of viral antigens and host factors is key to developing effective therapies.
Purpose of the Study:
- To investigate whether HIV-specific CD8 T cell clonotypes can be stimulated by allogeneic Human Leukocyte Antigen (HLA) molecules.
- To explore the potential of allo-HLA stimulation for enhancing HIV-specific T cell responses.
Main Methods:
- Derivation of multiple HIV-specific CD8 T cell clones from individuals with chronic HIV infection.
- Assaying T cell clones for alloreactivity against single HLA class I expressing cell lines (SALs).
- Measuring T cell responses via IFNγ production, CD137 upregulation, and cytotoxicity.
Main Results:
- HIV-specific T cells recognizing at least one allogeneic HLA molecule were identified in 7 out of 12 patients.
- Allorecognition was associated with significant immune responses, including cytokine production and cytotoxicity.
- Allo-HLA recognition was specific to the HIV target peptide, HLA restriction, and T cell receptor (TCR) TRBV usage.
Conclusions:
- HIV-specific T cells exhibit cross-reactivity against allogeneic HLA molecules in an epitope- and TRBV-specific manner.
- Allo-HLA stimulation represents a potential therapeutic strategy to induce or augment HIV-specific T cell responses.
- This finding opens new avenues for immunotherapy in HIV treatment.