Positive and negative CD4+ thymocyte selection by a single MHC class II/peptide ligand affected by its expression level in the thymus.
The central event in thymic selection of T cells bearing alpha beta TCRs is their interaction with self-peptides bound to self-MHC molecules. With the use of transgenic mouse lines expressing a single peptide/MHC class II complex, we show that CD4+ T cells with the preferential usage of particular TCR V(alpha)s and V(beta)s were selected to mature on this complex in lines with the lower expression, whereas such CD4+ T cells were eliminated in the thymus in a line with the relatively high expression. When a low expressing line was crossed with a high expressing line, the frequency of CD4+ T cells selected by this complex markedly decreased. Thus, these results suggest that a single peptide/MHC class II complex, being affected by its cell surface density in the thymus, can serve as both positively and negatively selecting ligand in vivo.
Fukui
Y
Y
Department of Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
Ishimoto
T
T
Utsuyama
M
M
Gyotoku
T
T
Koga
T
T
Nakao
K
K
Hirokawa
K
K
Katsuki
M
M
Sasazuki
T
T
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D000941:Antigens; D015703:Antigens, CD; D000943:Antigens, Differentiation; D000954:Antigens, Surface; D001483:Base Sequence; D051927:CD24 Antigen; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016827:CD8 Antigens; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D037181:Lectins, C-Type; D008024:Ligands; D007959:Lymphocyte Culture Test, Mixed; D008221:Lymphoid Tissue / Q000378:metabolism; D008562:Membrane Glycoproteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D055651:NK Cell Lectin-Like Receptor Subfamily B; D010452:Peptide Biosynthesis; D010455:Peptides / Q000276:immunology* / Q000502:physiology; D011506:Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D013154:Spleen / Q000166:cytology; D016176:T-Lymphocyte Subsets / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000378:metabolism*
D000941:Antigens; D015703:Antigens, CD; D000943:Antigens, Differentiation; D000954:Antigens, Surface; D051927:CD24 Antigen; D016827:CD8 Antigens; C497890:Cd24a protein, mouse; D000949:Histocompatibility Antigens Class II; D037181:Lectins, C-Type; D008024:Ligands; D008562:Membrane Glycoproteins; D055651:NK Cell Lectin-Like Receptor Subfamily B; D010455:Peptides; D011506:Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta