Oligoclonality of TCR^int Cells with a Low Diversity of TCR Complementarity‐Determining Region 3 in Mice with Graft‐ Versus‐Host Disease

Abstract

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 Vbeta8.2+ 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-->(B6xC3H/He)F1 and syngeneic BMT, B6-->B6. In these combinations, only TCRint cells were generated. Vbeta8.2+ cells with a low diversity of CDR3 of V-gene expanded in GVHD mice. Vbeta8.2+ 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 (bml2 mice) were injected into 1 Gy-irradiated B6 nude mice. Some Vbeta8.2+ 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 V alpha14, these results suggest that TCRint cells have a low diversity of CDR3 of Vbeta genes.

Vβ Usage and T Regulatory Cells in Children Following Partial or Total Thymectomy after Open Heart Surgery in Infancy

“…Sugahara et al. found evidence of oligodiversity and oligoclonality of TCR expressed by extrathymic T cells, indicating that the extrathymic microenvironment could alter gene usage and influence repertoire [14], but more evidence is needed.…”

“…On the other hand, thymus-independent T-cell reconstitution is characterized by T-cell monoclonal expansion with a restricted repertoire [12,13]. Sugahara et al found evidence of oligodiversity and oligoclonality of TCR expressed by extrathymic T cells, indicating that the extrathymic microenvironment could alter gene usage and influence repertoire [14], but more evidence is needed.…”

Unconventional NK1.1 intermediate TCR cells as major T lymphocytes expanding in chronic graft-versus-host disease

“…This autoreactivity of unconventional T cells may be due to their primordial nature. We reported the oligoclonality (mainly V g 8.2 + ) and low levels of the N region insertion in unconventional T cells [23].…”