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CD8 memory, immunodominance, and antigenic escape.

D Wodarz¹, M A Nowak

¹Institute for Advanced Study, Princeton, NJ 08540, USA.

European Journal of Immunology

|September 29, 2000

Summary

Efficient memory cytotoxic T lymphocyte precursors (CTLp) ensure long-term virus control by maintaining a broad T cell response. Short-lived CTLp lead to narrow responses, enabling rapid viral escape and loss of control.

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Area of Science:

Immunology
Virology
Mathematical Biology

Background:

Efficient virus control relies on persistent memory cytotoxic T lymphocyte precursors (CTLp).
Failure to generate memory CTLp can lead to persistent infections and loss of viral control.
The relationship between CTL response, viral escape, and infection persistence requires further investigation.

Purpose of the Study:

To investigate the link between virus control, CTL response clonal composition, and viral antigenic escape evolution.
To model the impact of memory CTLp persistence on viral dynamics and immune evasion.

Main Methods:

Utilized mathematical modeling to simulate CTLp dynamics and viral evolution.
Analyzed the clonal composition of CTL responses under different memory persistence scenarios.
Examined the probability and timescale of viral antigenic escape.

Main Results:

Efficient, antigen-independent memory CTLp sustain broad CTL responses, controlling viruses at low levels.
Broad CTL responses targeting multiple epitopes significantly delay viral antigenic escape.
Short-lived CTLp result in narrow, immunodominant responses, promoting rapid viral replication and escape.
Rapid viral escape leads to progressive loss of virus control.

Conclusions:

Sustained, antigen-independent memory CTLp are crucial for effective, long-term virus control.
The breadth of the CTL response, dictated by memory CTLp persistence, is a key factor in preventing viral escape.
Findings have implications for understanding persistent viral infections like HIV-1.

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