Oligoclonality of TCR[sup int] Cells with a Low Diversity of TCR Complementarity-Determining...

Conventional T cells (i.e. TCRhigh) are generated by the main stream of T-cell differentiation in the thymus. However, primordial T cells (i.e. TCRint) are generated by extrathymic pathways and an alternative intrathymic pathway. Since TCRint cells contain self-reactive clones, the diversity of the T-cell antigen receptor (TCR) complementarity-determining region (CDR) 3 was examined. The predominant Vβ8.2+ clones among TCRint cells were selected for DNA sequencing. Thymectomized, irradiated mice subjected to bone-marrow transplantation (BMT) were used; graft-versus-host disease (GVHD), B6→(B6 × C3H/He)F1 and syngeneic BMT, B6→B6. In these combinations, only TCRint cells were generated. Vβ8.2+ cells with a low diversity of CDR3 of V-gene expanded in GVHD mice. Vβ8.2+ cells of TCRint and TCRhigh cells in normal mice were polyclonal, showing that the former has a lower diversity of CDR3 than the latter. The clonality of activated TCRhigh cells was examined, in which CD3high cells (bm12 mice) were injected into 1 Gy-irradiated B6 nude mice. Some Vβ8.2+ clones among TCRhigh cells were expanding but the diversity of CDR3 was greater than that of CD3int cells, despite the fact that the recognition site of the H-2 difference was smaller. Taken together with invariant usage of Vα14, these results suggest that TCRint cells have a low diversity of CDR3 of Vβ genes. [ABSTRACT FROM AUTHOR]