Antigens coded for within the HLA complex play an important role in the control of immune responses. Presently, three major classes of HLA antigens can be defined: 1) Class I products, coded for by the HLA-A,B, and C loci, 2) Class II (Ia) products, coded for by the HLA-DR,DQ and DP loci and 3) Class III products which code for components involved in the complement cascade. Class I antigens are expressed by all mononuclear blood cells. Class II antigens, however, have a limited tissue distribution. They are expressed by B cells, monocytes, and by activated but not by resting T cells. It has long been appreciated that Class II (Ia) molecules expressed on monocytes and B cells are responsible for the regulation of the immune system. Specifically, they play a critical role 1) in antigen presentation, 2) in the communication between T cells and B cells and between T cells and macrophages, and 3) in influencing susceptibility to certain diseases. While Class II expression by activated T cells has not been well studied, recent evidence suggests that they may be involved in T cell function. For example, it was reported that the addition of anti-Class II monoclonal antibodies inhibited the proliferation of activated T cells. This suggested that Class II antigens on T cells might influence the transmission of signals which trigger cell proliferation and the development of functional ability. The principal aim of this proposal is to define the relationship between Class II gene expression and T cell activation and function. We will achieve our goal 1) by studying the transcription of the three types of Class II genes (DR, DQ, DP) in relation to two other genes turned on during T cell activation, the IL-2 molecule and its receptor (Tac), and in relation to the initiation of proliferation, 2) and by examining whether there are qualitative or quantitative differences in the accumulation of Class II mRNA by T cell clones with different functional activities. Elucidating the mechanism and significance of Class II gene expression in activated T cells will have major implications on the design of new approaches for immunomodulation in basic research, as well as in clinical settings.
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