Evidence that the leukocyte-common antigen is required for antigen-induced T lymphocyte proliferation
1Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110.
Insights
Leukocyte-common antigen (L-CA) is crucial for T cell activation. L-CA deficient T cells cannot proliferate in response to antigen, highlighting its role in initiating the cell cycle.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Leukocyte-common antigen (L-CA) is a family of glycoproteins found on hematopoietic cells.
- L-CA possesses a glycosylated exterior, a membrane-spanning region, and a cytoplasmic domain with tyrosine phosphatase activity.
Purpose of the Study:
- To investigate the function of L-CA in T cell activation.
- To determine the role of L-CA in T cell proliferation and cell cycle entry.
Main Methods:
- Generated T cell clones lacking L-CA (L-CA-).
- Assessed the expression of key T cell surface markers (TCR, CD3, CD4, IL-2 receptor, LFA-1, Thy-1, Pgp-1).
- Evaluated T cell proliferation in response to antigen, cross-linked CD3, and IL-2.
Main Results:
- L-CA- T cell clones showed normal expression of other T cell markers.
- L-CA- T cells failed to proliferate upon antigen or cross-linked CD3 stimulation.
- These cells could still proliferate in response to IL-2.
- Restoration of L-CA expression in a revertant clone re-established antigen- and CD3-induced proliferation.
Conclusions:
- L-CA is essential for T cells to initiate cell cycle progression in response to antigen stimulation.
- L-CA plays a critical role in T cell receptor signaling pathways leading to proliferation.
Abstract:
The leukocyte-common antigen (L-CA) is a family of large molecular weight glycoproteins uniquely expressed on the surface of all nucleated cells of hematopoietic origin. The glycoprotein consists of a heavily glycosylated exterior domain, a single membrane spanning region, and a large cytoplasmic domain that contains tyrosine phosphatase activity. To investigate the function of this family, we generated T cell clones that lacked L-CA (L-CA-). The expression of the alpha beta T cell receptor, CD3, CD4, IL-2 receptor (p55), LFA-1, Thy-1, and Pgp-1 (CD44) was normal. The L-CA- T cell clones failed to proliferate in response to antigen or cross-linked CD3; however, they could still proliferate in response to IL-2. An L-CA+ revertant was obtained and the ability to proliferate in response to antigen and cross-linked CD3 was restored. These data indicate that L-CA is required for T cells to enter into cell cycle in response to antigen.
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