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-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.
Sugahara
S
S
Department of Immunology, Niigata University School of Medicine, Japan.
Kuwano
Y
Y
Sato
K
K
Hasegawa
K
K
Yamagiwa
S
S
Kawamura
T
T
Yoshida
Y
Y
Asakura
H
H
Abo
T
T
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D016026:Bone Marrow Transplantation / Q000276:immunology; D002908:Chronic Disease; D022801:Complementarity Determining Regions; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D007137:Immunoglobulin alpha-Chains / Q000235:genetics*; D008099:Liver / Q000166:cytology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D022801:Complementarity Determining Regions; D007135:Immunoglobulin Variable Region; D007137:Immunoglobulin alpha-Chains; D016693:Receptors, Antigen, T-Cell, alpha-beta