involvement in the elimination of negatively selected T lymphocytes. MHC restriction within TNCs Whether the thymocytes undergo positive or negative selection is determined through MHC restriction, which refers to the interaction between the αβTCR (αβ T cell receptor) of the T cells and MHC antigens on the antigen-presenting cells. This role of MHC restriction was observed in a study conducted by Martinez et al. in HY-TCR transgenic mice. Since HY is a male specific antigen, the developing thymocytes would be expected to undergo degradation in males but not in females. However, both males and females were found to contain TNCs. Furthermore, female mice TNCs were found to contain five times more thymocytes than male mice, and less than 4% of them were apoptotic compared to almost 50% in the male TNCs. Also, almost 90% of all thymocytes extracted from the female TNCs were found to be double positives (CD4+CD8+), whereas no such phenotype was present within the male thymic nurse cells. Thus, since not all thymocytes internalized by TNCs went through apoptotic pathways, this was used to conclude that thymic nurse cells are involved in MHC restriction process. Negative selection has been proposed to occur when the αβTCR in developing T cells interact with MHC present on antigen-presenting cells like dendritic cells and macrophages with strong affinities, which then leads T cells down the apoptotic pathway inside the TNCs. Similarly, extremely weak affinities lead to the death of T lymphocytes through neglect. Only intermediate affinity interaction between the αβTCR of the T cells and MHC antigens in the TNCs results in positive selection. Thymocytes uptake The thymic cortical cells take up early thymocytes migrating from the bone marrow to the thymus and form the thymocyte-TNC complexes. The formation of finger-like projections has been found to facilitate this uptake; which also requires the participation of membrane and cytoskeleton proteins of TECs and thymocytes. Other players that mediate this process are ICAM-1, which is a cell adhesion molecule found on the surface of vacuoles and TNCs, and other extracellular glycoproteins like fibronectin, laminin and type IV collagen, which are produced by TNCs. Similarly, the cytoplasmic vacuoles present in the cytoplasm near the membrane network also facilitate the uptake of thymocytes that have been negatively selected to undergo apoptosis. The molecules like gal-3 (Galectin-3) and gal-1(Galectin-1), on the other hand, produce antagonistic effects. They inhibit thymocytes/TEC interaction and affect the movement of thymocytes