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.
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.
authors.affiliation: Department of Microbiology and Immunology, University of British Columbia, Vancouver, Canada.
authors.forename: H S
authors.initials: HS
authors.lastname: Teh
authors.forename: B
authors.initials: B
authors.lastname: Motyka
authors.forename: S J
authors.initials: SJ
authors.lastname: Teh
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology; D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics; D051927:CD24 Antigen; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D003433:Crosses, Genetic; D006183:H-2 Antigens / Q000235:genetics / Q000378:metabolism*; D016130:Immunophenotyping; D008024:Ligands; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics; D008562:Membrane Glycoproteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis* / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism*
chemical_list: D000941:Antigens; D015703:Antigens, CD; D051927:CD24 Antigen; C497890:Cd24a protein, mouse; D006183:H-2 Antigens; D008024:Ligands; D008562:Membrane Glycoproteins; D011948:Receptors, Antigen, T-Cell