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Updated: Apr 10, 2026

Purification of the Membrane Compartment for Endoplasmic Reticulum-associated Degradation of Exogenous Antigens in Cross-presentation
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Perforin-2 enhances antigen-specific CTL immune response by promoting cross presentation

Zhi-Kai Zha1, Cheng-Jie Deng2, Ling-Jun Shen3

  • 1Yunnan Provincial Key Laboratory of Public Health and Bio-safety & Department of Pathogen Biology and Immunology, Faculty of Basic Medical Science, Kunming Medical University, Kunming, China.

Cell Death & Disease
|April 8, 2026
PubMed

Insights

Perforin-2 (P2) is crucial for dendritic cell cross-presentation of antigens, supporting CD8+ T cell immunity. Its absence weakens anti-tumor responses and antigen uptake, highlighting P2

Area of Science:

  • Immunology
  • Cell Biology

Background:

  • Antigen cross-presentation by dendritic cells (DCs) is vital for initiating CD8+ cytotoxic T lymphocyte (CTL) responses.
  • Perforin-2 (P2), a pore-forming protein in DCs, is suggested to aid endocytic cargo escape, but its role in cross-presentation is unclear.

Purpose of the Study:

  • To investigate the role of Perforin-2 (P2) in dendritic cell (DC)-mediated antigen cross-presentation.
  • To elucidate the mechanisms by which P2 influences antigen uptake and processing for CD8+ T cell activation.

Main Methods:

  • Utilized P2 knockout (P2-/-) mice to assess DC function and T cell responses.
  • Analyzed antigen cross-presentation of soluble and particulate antigens.
  • Investigated P2's impact on T cell immunity in melanoma models.
  • Examined P2's role in antigen uptake mechanisms (macropinocytosis) and endosomal pH regulation.

Main Results:

  • Loss of P2 significantly impaired DC cross-presentation of various antigens.
  • P2 deficiency led to reduced antigen-specific CD8+ T cell responses.
  • P2-/- mice showed defective endogenous CTL responses and diminished anti-tumor immunity.
  • Mechanistically, P2 facilitates antigen uptake via membrane-repair-mediated macropinocytosis and limits excessive endosomal acidification.

Conclusions:

  • Perforin-2 (P2) is a key regulator of antigen cross-presentation and CD8+ T cell immunity.
  • P2 coordinates antigen uptake and processing, essential for effective immune responses against tumors.

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