The CD8 co-receptor interacts with nonpolymorphic residues on class I molecules. L(Q3), a laboratory engineered L(d) molecule bearing an α3 domain derived from Q7 (Qa-2), interacts poorly with anti-L(d) CD8-dependent T cells. 2C TCR transgenic mice bear a receptor specific for the p2Ca peptide bound to L(d). The authors show that although this peptide interacts with L(Q3), L(Q3) APC fail to activate splenic 2C CD8 T cells in vitro in the absence of IL-2, while control L(d) APC do. The authors have used this receptor ligand pair to examine negative selection within the thymus of (B6 x C3H.L(d))F1 versus (B6 x C3H.L(Q3))F1 radiation chimeras repopulated with 2C bone marrow cells. While positive selection occurs normally in (B6 x C3H)F1 chimeras, animals expressing either L(d) or L(Q3) full to generate 2C CD8+ cells. Thus, either CD8 is not required for negative selection of this TCR or a weak interaction of CD8 with L(Q3) is sufficient. TSA-1, a developmentally regulated marker, was used to follow the process of negative selection. The results show that deletion of 2C T cells does not occur until thymocytes reach the double positive (DP) stage. Furthermore, the authors noted a small population of DP TSA- I(hi) cells remains, while DP TSA- 1(int) and TSA- 1(lo) cells are absent. These data support the notion that thymocytes either reach a particular stage of development or locate in an appropriate intrathymic compartment before they undergo negative selection.
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