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show that lower TCR expression in thymocytes contributes to effecting these differences. An analogy with the phase behavior of simple fluids helps clarify how, for low TCR expression, thermal fluctuations lead to the dynamic synapse patterns observed for thymocytes. We suggest that a different synapse pattern resulting from lower TCR expression, which could mediate differential signaling, may be the reason why TCR expression level is low in thymocytes.A ctivation of mature T lymphocytes (T cells) in response to pathogens and the maturation and selection of immature T cells (thymocytes) in the thymus leading to the available T cell repertoire are key features of an adaptive immune system (1). Antigen-presenting cells (APCs) catabolize pathogen-derived protein into small peptide fragments. These peptides can bind to proteins coded for by the major histocompatibility gene, and the resulting complexes [MHC peptide (MHCp)] are then displayed on the APC surface. Binding of T cell receptor (TCR) molecules expressed on the T cell surface to these MHCp complexes initiates intracellular signaling cascades that can activate mature T cells (2), resulting in effector functions such as cytokine production, proliferation, and killing of target cells (3,4).Recent in vitro and in vivo experiments have demonstrated that during mature T cell activation different types of receptors and ligands segregate to different regions of the T cell-APC junction (5-13). The resulting spatial pattern of receptors and ligands is called the immunological synapse. A temporally stable mature immunological synapse forms in many minutes and is characterized (Fig. 1a) by a central accumulation of TCR and MHCp (cSMAC) and a peripheral ring of adhesion molecules (pSMAC). A number of recent studies have provided partial answers to the question of how the synapse forms (5-19), but its role in T cell activation is not well understood.Thymocyte selection and maturation in the thymus also requires binding of TCR to MHCp complexes displayed on thymic APCs (20). The peptides in this case are derived from proteins characteristic of the organism (self-peptides). Thymocytes undergo either positive or negative selection after TCR-MHCp binding (20)(21)(22)(23)(24). Positive selection is a step toward the development of mature T cells, whereas negative selection corresponds to apoptosis triggered by strong TCR-MHCp binding. Some details of signaling during thymocyte development and mature T cell activation are different (25). However, because most of the initial molecular players and signaling pathways involved in mature T cell activation and thymocyte selection are the same, an important question emerges: Why are the biological consequences of similar signaling cascades initiated by TCR-MHCp binding different in the two cases? This question has motivated recent experiments (26-28) that examine whether synapse patterns at thymocyte-APC junctions are different from those observed during mature T cell activation.In vitro experiments have been carried out with CD4 ϩ CD...