Oligoclonality of TCRint Cells with a Low Diversity of TCR Complementarity-Determining Region 3 in Mice with Graft- Versus-Host Disease

Conventional T cells (i.e. TCR^high) are generated by the main stream of T-cell differentiation in the thymus. However, primordial T cells (i.e. TCR^int) are generated by extrathymic pathways and an alternative intrathymic pathway. Since TCR^int 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 TCR^int 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) F ₁ and syngeneic BMT, B6→B6. In these combinations, only TCR^int cells were generated. Vβ8.2⁺ cells with a low diversity of CDR3 of V-gene expanded in GVHD mice. Vβ8.2⁺ cells of TCR^int and TCR^high cells in normal mice were polyclonal, showing that the former has a lower diversity of CDR3 than the latter. The clonality of activated TCR^high cells was examined, in which CD3^high cells (bm12 mice) were injected into 1 Gy-irradiated B6 nude mice. Some Vβ8.2⁺ clones among TCR^high cells were expanding but the diversity of CDR3 was greater than that of CD3^int 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 TCR^int cells have a low diversity of CDR3 of Vβ genes.