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. TCRhigh) are generated by the main stream of T-c ell differentiation in the thymus. However, primordial T cells (i.e. TCRint ) are generated by extrathymic pathways and an alternative intrathymic path way. Since TCRint cells contain self-reactive clones, the diversity of the T-cell antigen receptor (TCR) complementarity-determining region (CDR) 3 wa s examined. The predominant V beta 8.2(+) clones among TCRint cells were se lected for DNA sequencing. Thymectomized, irradiated mice subjected to bone -marrow transplantation (BMT) were used; graft-versus-host disease (GVHD), B6-->(B6 x C3H/He)F-1 and syngeneic BMT, B6-->B6. In these combinations, on ly TCRint cells were generated. V beta 8.2(+) cells with a low diversity of CDR3 of V-gene expanded in GVHD mice. V beta 8.2(+) cells of TCRint and TC Rhigh cells in normal mice were polyclonal, showing that the former has a l ower diversity of CDR3 than the latter. The clonality of activated TCRhigh cells was examined, in which CD3(high) cells (bm12 mice) were injected into 1 Gy-irradiated B6 nude mice. Some V beta 8.2(+) clones among TCRhigh cell s 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 w as smaller. Taken together with invariant usage of V alpha 14, these result s suggest that TCRint cells have a low diversity of CDR3 of V beta genes.