Functional characterization of an antigen involved in an early step of T-cell activation.

Abstract

An activation antigen, identified by the monoclonal antibody MLR3, is described that is present on activated T lymphocytes and thymocytes but not on resting T lymphocytes. Immunoprecipitation of radiolabeled membranes from an activated T-cell line showed that the MLR3-binding molecule has a molecular size of 28-34 kDa. Immunofluorescence analysis showed that the appearance of the MLR3 antigen is an early event and precedes that of the interleukin 2 receptor both in T lymphocytes and thymocytes. The proliferative response of resting T cells to OKT3-Sepharose and interleukin 1 or accessory cells, but not the interleukin 2-dependent proliferation, was inhibited by the addition of MLR3 monoclonal antibodies. Similar results were also obtained in an interleukin 1-dependent human thymocyte proliferation assay. In addition when MLR3-positive cells were cultured with purified interleukin 1, MLR3 surface antigen expression was not observed. Thus MLR3 monoclonal antibody appears to recognize an antigen involved in an early step of T-cell activation related to interleukin 1-dependent functions and on both T lymphocytes and thymocytes.T-cell activation is a multistep process induced by the interaction of the Ti-T3 complex with the antigen in the presence of self-major histocompatibility complex-encoded molecules (1-3). Triggering of this complex ultimately results in cell proliferation mediated by the interaction of interleukin 2 (IL-2) with its receptor on the cell surface (4-7). Between the interaction with the antigen and the IL-2-mediated proliferation, a series of signals are delivered by factors such as colony stimulating factor, interleukin 1 (IL-1), IL-2, and interferon-y (8-1 1). At the same time, a number of membrane structures with receptor function are expressed on the surface of activated T cells and mediate communication with the environment (6,7,(12)(13)(14)(15). In antigen-mediated T-cell activation, the collaboration with accessory cells (AC) (macrophages and B cells) is crucial, at least for the HLA class II-restricted T cells, since AC provide the system with both membrane determinants and soluble factors necessary for a successful completion of the entire T-cell activation process (3,(16)(17)(18). Among soluble factors, IL-1 seems to play a key role in T-cell activation (19, 20); however, the precise role of AC membranes and AC-derived cytokines is still debated and its definition awaits a more subtle dissection (18,(21)(22)(23)(24). Monoclonal antibodies (mAbs) that recognize molecular structures expressed on T-cell membranes in early phases of activation and that are able to interfere with their function are important tools in dissecting the multiple events occurring after antigen triggering. In this paper, we have studied the mouse mAb MLR3 that recognizes an antigen present on activated but not on resting T cells (25). Our data show that MLR3 mAb is able to inhibit the polyclonal T-cell proliferation induced by anti-T3 mAb (OKT3) coupled to Sepharose and by IL-1 or AC but fails to affect IL-2...

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