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Published on: February 28, 2019
Phytohemagglutin-stimulated human T cell: prothymosin alpha as an accessory signal
O J Cordero1, C S Sarandeses, M Nogueira
1Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Santiago, Santiago de Compostela, Spain.
Insights
Prothymosin alpha (Pro alpha) and thymosin alpha 1 (alpha 1) modulate human lymphocyte proliferation, with effects varying by stimulation and dose. Thymosin beta 4 (beta 4) showed no impact, serving as a control.
Area of Science:
- Immunology
- Molecular Biology
Background:
- Thymic peptide factors are crucial for regulating normal human lymphocyte proliferation.
- Understanding the specific roles of thymosins in immune responses is essential for therapeutic development.
Purpose of the Study:
- To investigate the impact of Prothymosin alpha (Pro alpha) on phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMC) and peripheral blood lymphocyte cultures (PBLC).
- To evaluate the role of thymosin alpha 1 (alpha 1) and thymosin beta 4 (beta 4) in lymphocyte proliferation.
- To elucidate the involvement of macrophages and interleukin-1 (IL-1) in Pro alpha-mediated lymphoproliferation.
Main Methods:
- Culturing of PHA-stimulated PBMC and PBLC with varying concentrations of Pro alpha, alpha 1, and beta 4.
- Assessing lymphoproliferative responses under different stimulation levels and preincubation times.
- Investigating the role of monocytes and monocyte-derived supernatants.
- Evaluating the effects of IL-1 and an IL-2 receptor antagonist (Tac Ag) on T cell proliferation.
Main Results:
- Pro alpha and alpha 1 demonstrated dose- and time-dependent modulation of PBMC proliferation.
- Thymosin beta 4 did not affect lymphocyte proliferation, validating its use as a control peptide.
- Macrophage presence was critical for Pro alpha-induced lymphoproliferation.
- IL-1 enhanced Pro alpha's helper effect, and this combined effect was blocked by an IL-2 receptor antagonist, indicating an IL-2-dependent pathway.
Conclusions:
- Pro thymosin alpha and thymosin alpha 1 are potent modulators of human lymphocyte proliferation, with their activity influenced by cellular context and stimulation.
- Macrophage-derived factors and IL-2 signaling pathways are integral to the lymphoproliferative effects of Pro alpha.
- Thymosin beta 4 serves as a useful control peptide in studies of thymosin function.
Abstract:
Thymic peptide factors are known to modulate proliferation of normal human lymphocytes. In this work, we studied the effect of Prothymosin alpha (Pro alpha) on PHA-stimulated PBMC and PBLC. The observed effects of Pro alpha and thymosin alpha 1 (alpha 1) on PBMC were found to depend on the degree of cell stimulation, dose, and preincubation-time. Thymosin beta 4 (beta 4) had no effect on either cell type, regardless of the degree of stimulation, which shows that beta 4 may be used as a control peptide to work in this area. Induction of lymphoproliferation also depended on the presence of macrophages. Addition of monocytes or a cell-free monocyte culture supernatant (not containing IL-2) to the PHA-stimulated PBLC cultures resulted in T cell proliferation. Although IL-1 could not restore the PHA-induced proliferative response of isolated T cells by itself, it would enhance the helper effect of Pro alpha. Moreover, a polyclonal goat anti-human IL-2R (Tac Ag) did block the proliferative response induced by combined rIL-1 and Pro alpha, suggesting that an IL-2-dependent pathway of T cell proliferation was involved.
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