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  • Title: Positive selection of thymocytes expressing the same TCR by different MHC ligands results in the production of functionally distinct thymocytes distinguished by differential expression of the heat stable antigen.
    Author: Teh HS, Motyka B, Teh SJ.
    Journal: J Immunol; 1998 Jan 15; 160(2):718-27. PubMed ID: 9551907.
    Abstract:
    The issue of whether the signaling process during positive selection can affect the efficiency by which the positively selected T cells respond to antigenic stimulation has not been addressed. We approached this question by determining the consequences of positive selection of a particular transgenic TCR (2C TCR) in the H-2b and the H-2k thymus. The H-2b thymus provides a strong positive-selecting environment for the 2C TCR, whereas the H-2k thymus selects weakly for the 2C TCR. Although the positively selected CD8 thymocytes from the H-2b or H-2k thymus expressed similar levels of the CD8 coreceptor molecule, those for the H-2k thymus expressed a slightly lower level of the 2C TCR. This lower level of 2C TCR expression by H-2k CD8 thymocytes was not a result of coexpression of endogenous TCRs. Interestingly, CD8 thymocytes from H-2k mice were hyporesponsive to Ag stimulation compared with those from the H-2b mice. The functional maturity of positively selected CD8 thymocytes from the H-2b or H-2k thymus was inversely correlated with the level of heat stable Ag expressed by these cells. Furthermore, TCR-derived signals appear to be more efficiently coupled to downstream pathways leading to proliferation and cytokine production in CD8 thymocytes from H-2b 2C mice than those derived from H-2k 2C mice. These results provide the first demonstration that the intensity of the signaling process during positive selection affects the efficiency by which TCR-derived signals in positively selected thymocytes are coupled to downstream effector pathways.
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