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Activation-induced expression of MICA on T lymphocytes involves engagement of CD3 and CD28
Luciana L Molinero1, Mercedes B Fuertes, Gabriel A Rabinovich
1Laboratorio de Inmunogenética, Hospital de Clínicas José de San Martín, Facultad de Medicina, Universidad de Buenos Aires, Av. Cordoba 2351, 3er piso, 1120 Buenos Aires, Argentina.
Abstract:
MICA is an HLA-related cell stress-regulated antigen recognized by cytotoxic cells expressing the NKG2D molecule. Although resting lymphocytes do not express MICA, it can be induced on PHA-activated T cells. Here, we demonstrate by Western blot that MICA is induced on allogeneic-activated CD4(+) and CD8(+) T lymphocytes. Blocking activation with anti-HLA class I, anti-HLA-DR, or anti-CD86 mAb affected the expression of MICA slightly. When T cells were stimulated with anti-CD3 or anti-CD28 mAb plus PMA, a sustained up-regulation of MICA was observed by Western blot, RT-PCR, and flow cytometry. The expression of MICA reached a plateau at day 4 after CD3 engagement and at day 3 after anti-CD28/PMA stimulation. Conversely, the proliferative response reached a peak at day 4. Hence, CD3 or CD28 engagement induces MICA expression on T lymphocytes. This activation-induced expression might participate in NKG2D-mediated cytotoxicity toward activated T cells to maintain homeostasis during an ongoing immune response.
Insights
T cell activation via CD3 or CD28 signaling upregulates MICA expression. This induction may play a role in NKG2D-mediated killing of activated T cells, aiding immune response homeostasis.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- MICA (MHC class I polypeptide-related sequence A) is an antigen recognized by NKG2D receptors on cytotoxic cells.
- MICA is typically absent on resting lymphocytes but can be induced upon T cell activation.
Purpose of the Study:
- To investigate the induction of MICA expression on T lymphocytes.
- To determine the role of T cell receptor (TCR) and co-stimulatory signals in MICA upregulation.
Main Methods:
- Western blot analysis
- Reverse transcription polymerase chain reaction (RT-PCR)
- Flow cytometry
- T cell activation using anti-CD3, anti-CD28, and PMA
Main Results:
- MICA was induced on both CD4(+) and CD8(+) T lymphocytes upon allogeneic activation.
- Stimulation with anti-CD3 or anti-CD28 antibodies plus PMA led to sustained MICA upregulation.
- MICA expression peaked around day 3-4 post-stimulation, correlating with T cell proliferation.
Conclusions:
- CD3 and CD28 engagement are key drivers of MICA expression on activated T cells.
- Activation-induced MICA expression may contribute to NKG2D-mediated cytotoxicity against activated T cells, promoting immune homeostasis.