TAP-ing into the cross-presentation secrets of dendritic cells

Area of Science:

• Immunology
• Virology
• Cell Biology

Background:

• Viruses block the transporter associated with antigen processing (TAP) in dendritic cells (DCs).
• This blockade reduces major histocompatibility complex class-I (MHC-I) on DCs, impairing CD8 T-cell responses.
• Existing cross-presentation mechanisms are insufficient against viruses that downregulate TAP.

Purpose of the Study:

• To investigate a noncanonical cross-presentation pathway in DCs.
• To determine if this pathway can overcome viral TAP blockade.
• To assess its potential for priming CD8 T cells against immune-evasive pathogens and cancers.

Main Methods:

• Utilized dendritic cells with viral blockade of the transporter associated with antigen processing (TAP).
• Analyzed major histocompatibility complex class-I (MHC-I) presentation and CD8 T-cell priming.
• Investigated viral peptide presentation independent of canonical pathways.

Main Results:

• Noncanonical cross-presentation in DCs bypasses cell-intrinsic TAP blockade.
• This pathway effectively primes protective CD8 T cells against TAP-independent epitopes.
• These T cells are well-matched to infections with immune-evasive viruses.

Conclusions:

• Noncanonical cross-presentation offers a strategy to overcome viral immune evasion.
• Exploiting this pathway could lead to treatments for chronic viral infections.
• It may also provide a novel approach for controlling TAP-downmodulated cancers.