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Monomorphic molecules function as additional recognition structures on haptenated target cells for HLA-A1-restricted,
J Stöckl1, O Majdic, G Fischer
1Institute of Immunology, University of Vienna, Medical School, Vienna, Austria. Johannes.Stoeckl@univie.ac.at
Journal of Immunology (Baltimore, Md. : 1950)
|August 18, 2001
Summary
High antigen doses enable trinitrophenyl (TNP)-specific CD8(+) cytotoxic T lymphocytes (CTL) to recognize target cells independently of the major histocompatibility complex (MHC). This novel recognition involves direct CD39 molecule interaction, mediated by the T cell receptor (TCR).
Area of Science:
- Immunology
- Cellular Biology
- T Cell Recognition Mechanisms
Background:
- Hapten-specific T cells typically recognize haptenated peptides with high avidity.
- Previous studies indicated promiscuous MHC restriction in some hapten-specific T cell responses.
- The influence of antigen (Ag) density on MHC restriction in cytotoxic T lymphocyte (CTL) responses remained unclear.
Purpose of the Study:
- To investigate the impact of antigen density on MHC restriction of a CTL response specific to the trinitrophenyl (TNP) hapten.
- To elucidate novel recognition mechanisms employed by TNP-specific CD8(+) CTL at high antigen doses.
Main Methods:
- Investigated TNP-specific CD8(+) CTL activity in response to varying TNP epitope densities on target cells.
- Utilized T cell receptor (TCR) mediated recognition assays.
- Examined the role of cell surface molecules, including CD39, in target cell recognition.
Main Results:
- At low TNP epitope levels, CTL activity was restricted to HLA-A1.
- At high TNP loading, entirely MHC-independent target cell recognition by CTLs became operational.
- Both MHC-restricted and MHC-independent recognition pathways were TCR-mediated.
- MHC-independent recognition involved direct interaction with the ectonucleotidase family surface molecule CD39.
- This MHC-independent recognition was restricted by target cell type.
Conclusions:
- Antigen density significantly modulates MHC restriction in hapten-specific CTL responses.
- A novel TCR-dependent, MHC-independent recognition pathway exists for TNP-specific CD8(+) CTLs at high antigen loads.
- Direct recognition of CD39 by CTLs represents a key mechanism in this MHC-independent pathway.