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HLA-Ig Based Artificial Antigen Presenting Cells for Efficient ex vivo Expansion of Human CTL
Published on: April 11, 2011
Partial activation of CD8+ T cells by a self-derived peptide
1Beirne B. Carter Center for Immunology Research, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
Nature
|November 16, 1995
Summary
Structural changes in peptides presented by major histocompatibility complex (MHC) molecules can selectively trigger CD95-CD95L-mediated killing in CD8+ T cells, independent of the perforin pathway.
Area of Science:
- Immunology
- Molecular Biology
- Cellular Biology
Background:
- T cell activation typically requires specific peptide presentation by major histocompatibility complex (MHC) molecules.
- Structural variants of immunogenic peptides can modulate T cell responses, including partial activation or antagonism.
- CD8+ T cells utilize perforin-dependent granule exocytosis and CD95-CD95L interactions for target cell lysis.
Purpose of the Study:
- To investigate the differential killing mechanisms of CD8+ T cells when stimulated by structurally similar peptides.
- To determine if CD95-CD95L-mediated killing can be triggered independently of the perforin pathway.
- To explore the impact of minor peptide structural changes within the MHC-binding groove on T cell cytotoxicity.
Main Methods:
- Utilized a clone of Kd-restricted CD8+ T cells specific for influenza hemagglutinin.
- Stimulated T cells with both a myeloma tumor immunoglobulin heavy-chain variable region (IgVH) peptide and its germline counterpart.
- Analyzed the killing pathways employed (perforin-dependent vs. CD95-CD95L) under different peptide stimulation conditions.
Main Results:
- CD8+ T cells activated by the tumor IgVH peptide killed targets via both perforin and CD95-CD95L pathways.
- When stimulated by the germline IgVH peptide, which differs by a single amino acid in the MHC-binding groove, CD8+ T cells killed targets exclusively through the CD95-CD95L pathway.
- This demonstrates that CD95-CD95L-mediated killing can be selectively activated independently of perforin-dependent killing.
Conclusions:
- Minor alterations in peptide structure presented by MHC molecules can distinctly modulate CD8+ T cell cytotoxic mechanisms.
- The CD95-CD95L pathway offers a distinct and selectively triggerable route for CD8+ T cell-mediated cytotoxicity.
- Changes in MHC conformation, influenced by peptide binding, play a critical role in determining the specific cytotoxic pathway utilized by CD8+ T cells.
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