Evidence for a single-niche model of positive selection.
Thymocyte maturation depends on interactions with thymic stromal elements expressing major histocompatibility complex (MHC) molecules. Mutant mouse strains lacking MHC class I (beta 2-microglobulin-null) or class II (A beta-null) expression fail to generate normal CD8 or CD4 T-cell populations and provide model systems for reconstitution experiments. We have constructed in vitro chimeras between normal and MHC-deficient thymi to evaluate the efficiency of positive selection. Unexpectedly, the generation of mature single-positive thymocytes was proportional to the fraction of wild-type (i.e., MHC-expressing) stroma over a wide range of chimerism. Similar results were obtained for the development of T-cell receptor-transgenic thymocytes in graded chimeras expressing selecting and nonselecting MHC alleles. These findings are best explained by hypothesizing that positive selection involves a rate-limiting step at which each thymocyte can interact with only one stromal cell niche.
Laboratoire de Génétique Moleculaire des Eukaryotes, Centre National de la Recherche Scientifique, Strasbourg, France.
M
M
Merkenschlager
C
C
Benoist
D
D
Mathis
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D002454:Cell Differentiation; D002678:Chimera; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000502:physiology*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D013950:Thymus Gland / Q000166:cytology*; D001613:beta 2-Microglobulin / Q000502:physiology*
D000949:Histocompatibility Antigens Class II; D016693:Receptors, Antigen, T-Cell, alpha-beta; D001613:beta 2-Microglobulin