Latency reversal agents modulate HIV antigen processing and presentation to CD8 T cells.

Area of Science:

• Immunology
• Virology
• Molecular Biology

Background:

• Latency reversal agents (LRAs) re-express HIV in CD4 T cells but do not clear reservoirs.
• The impact of LRAs on HIV epitope presentation post-latency reversal is unknown.
• HIV peptide presentation relies on intracellular protein degradation, influenced by proteasomes and peptidases.

Purpose of the Study:

• To investigate how LRAs affect HIV antigen processing and epitope production in CD4 T cells.
• To determine if HIV epitope presentation differs between latency reversal and initial infection.
• To define immune responses capable of detecting HIV-infected cells after latency reversal.

Main Methods:

• Comparing the effects of HDAC inhibitors (HDCAi) and PKC agonists (PKCa) on cytosolic proteolytic activity in LRA-treated CD4 T cells.
• Analyzing the degradation patterns of long HIV peptides and the production of HIV epitopes.
• Assessing the impact of LRAs on HIV infection kinetics and CD8 T cell activation.

Main Results:

• HDAC inhibitors reduced proteolytic activity, while PKC agonists increased it, albeit less than TCR activation.
• HDACi and PKCa modulated HIV peptide degradation patterns and epitope production differently.
• HDACi narrowed HIV antigenic fragment coverage, whereas PKCa broadened it.
• PKC agonists enhanced endogenous epitope processing and presentation to CD8 T cells early in treatment.

Conclusions:

• LRA-induced modulation of antigen processing significantly alters HIV epitope presentation.
• Exploiting these LRA-mediated changes can enhance HIV peptide presentation and immune recognition after latency reversal.
• This approach may improve the detection of diseased cells beyond HIV.