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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 Antigen¹

Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada

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-2^b and the H-2^k thymus. The H-2^b thymus provides a strong positive-selecting environment for the 2C TCR, whereas the H-2^k thymus selects weakly for the 2C TCR. Although the positively selected CD8 thymocytes from the H-2^b or H-2^k thymus expressed similar levels of the CD8 coreceptor molecule, those for the H-2^k thymus expressed a slightly lower level of the 2C TCR. This lower level of 2C TCR expression by H-2^k CD8 thymocytes was not a result of coexpression of endogenous TCRs. Interestingly, CD8 thymocytes from H-2^k mice were hyporesponsive to Ag stimulation compared with those from the H-2^b mice. The functional maturity of positively selected CD8 thymocytes from the H-2^b or H-2^k 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-2^b 2C mice than those derived from H-2^k 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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