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A Colorimetric Assay that Specifically Measures Granzyme B Proteolytic Activity: Hydrolysis of Boc-Ala-Ala-Asp-S-Bzl
Published on: November 28, 2014
Granzyme C supports efficient CTL-mediated killing late in primary alloimmune responses
Yonas Getachew1, Heather Stout-Delgado, Bonnie C Miller
1Department of Internal Medicine, Division of Digestive and Liver Diseases, niversity of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|November 20, 2008
Summary
Granzyme C supports cytotoxic T lymphocyte (CTL) killing via the perforin pathway, especially when granzymes A and B are absent. This function becomes apparent after restimulation in late alloimmune responses.
Area of Science:
- Immunology
- Cellular Biology
Background:
- Cytotoxic T lymphocytes (CTLs) eliminate target cells through the perforin-dependent granule exocytosis pathway.
- Granzymes A and B are key mediators, but the roles of other granzymes are less understood.
Purpose of the Study:
- To investigate the role of granzyme C in CTL-mediated killing using mice deficient in dipeptidyl peptidase 1 (DPP1).
- To elucidate granzyme C's contribution to allogeneic target cell lysis in the absence of functional granzymes A and B.
Main Methods:
- Utilized CTLs from DPP1-deficient mice in mixed lymphocyte cultures (MLC) and in vivo models.
- Assessed cytotoxicity after initial sensitization and following restimulation.
- Employed small interfering RNA (siRNA) to inhibit granzyme C expression.
Main Results:
- DPP1(-/-) CTLs showed impaired cytotoxicity early in alloimmune responses.
- Restimulation significantly enhanced DPP1(-/-) CTL cytotoxicity to levels comparable to wild-type CTLs.
- Grancyme C expression increased upon restimulation, and its inhibition reduced DPP1(-/-) CTL killing.
Conclusions:
- Granzyme C can mediate CTL killing via the granule exocytosis pathway in late primary alloimmune responses, even without functional granzymes A or B.
- This highlights granzyme C's distinct role in adaptive immunity and CTL effector functions.
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