The functional CD8 T cell response to HIV becomes type-specific in progressive disease

Area of Science:

• Immunology
• Virology
• Molecular Biology

Background:

• High levels of HIV-specific CD8 T cells are detectable throughout HIV infection.
• While effective in acute stages, these CD8 T cells fail to control viral replication in chronic infection.
• Viral evolution under immune pressure may reduce the in vivo relevance of CD8 T cell responses to consensus epitopes.

Purpose of the Study:

• To investigate if CD8 T cells responding to consensus epitopes lose relevance in chronic HIV infection due to viral evolution.
• To compare CD8 T cell responses to lab-adapted HIV versus autologous HIV in different disease stages.

Main Methods:

• Assessing Interferon-gamma (IFN-gamma) responses to HIV-infected cells.
• Sequencing T cell receptor beta chain variable (TCRBV) genes to determine T cell receptor (TCR) clonotypes.
• Performing cytolytic assays to evaluate cross-recognition by T cell lines.

Main Results:

• IFN-gamma response magnitude decreased with disease progression, particularly to autologous virus.
• TCR clonotypes differed significantly between responses to lab-adapted HIV and autologous virus in symptomatic patients.
• T cell lines showed cross-recognition in asymptomatic donors but not in progressors with distinct TCR clonotypes.

Conclusions:

• In advanced HIV disease, viral-specific CD8 T cells recognizing consensus epitopes persist but fail to effectively recognize the autologous virus.
• Immune escape is driven by viral evolution, leading to divergent T cell receptor repertoires and reduced antiviral function in chronic infection.