Title

The role of Ly-6A/E alloantigens in the immune system: Ly-6A/E defines subsets of developing T cells and functions to regulate T and B lymphocyte activation

Date of Award

1990

Availability

Article

Degree Name

Doctor of Philosophy (Ph.D.)

Department

Microbiology and Immunology

First Committee Member

Thomas R. Malek, Committee Chair

Abstract

Ly-6 molecules are 12-18 kD phosphatidylinositol-anchored proteins encoded by a multigene family and expressed on the surface of lymphocytes and other cell types. One well characterized Ly-6 protein, Ly-6A/E, displays properties of both a differentiation antigen and an antigen involved in regulation of cellular activation. In this investigation studies were performed both to begin to define the potential role of Ly-6A/E as a differentiation antigen and to further investigate the biological function of Ly-6A/E proteins in activation of peripheral lymphocytes. To test whether Ly-6A/E expression was characteristic of a differentiation marker, Ly-6A/E expression was determined for T cells and thymocytes for both Ly-6 haplotypes. Ly-6A/E was consistently expressed on subsets of mature thymocytes and peripheral T cells and the pattern of expression seen in mature thymic subsets was also present in peripheral T cell subsets. These data suggest expression of Ly-6A/E on a particular T cell subset is established prior to exit from the thymus and is a stable characteristic of each haplotype, and are consistent with Ly-6A/E proteins marking a lineage or functional subset of T cells. In order to further investigate the function of Ly-6A/E in activation of peripheral lymphocytes, an anti-Ly-6A/E monoclonal antibody was used as a probe to mimic Ly-6 function in vitro. In studies testing whether Ly-6A/E modulates T cell receptor (TCR) signalling, anti-Ly-6A/E mAb specifically inhibited interleukin 2 production of T cells that were also activated through TCR. In studies testing whether Ly-6A/E molecules are functional for B cells, anti-Ly-6A/E, together with gamma interferon, modulated B cell proliferation to interleukin 4 and anti-IgM and upregulated cell surface expression of Ly-6A/E. These latter findings extend the immune modulatory capacity of Ly-6A/E proteins to B as well as T cells. Collectively, the capacity of anti-Ly-6A/E to modulate signals delivered through TCR for T cells and through gamma interferon receptor for B cells suggests the function of Ly-6A/E may be to amplify or regulate the response of lymphocytes activated through another cell surface receptor.

Keywords

Health Sciences, Immunology

Link to Full Text

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