Antigen/MHC-specific T cells are preferentially exported from the thymus in the presence of their MHC ligand.
Transgenic mice expressing a T cell receptor heterodimer specific for a fragment of pigeon cytochrome c plus an MHC class II molecule (I-Ek) have been made. We find that H-2k alpha beta transgenic mice have an overall increase in the number of T cells and express a 10-fold higher fraction of cytochrome c-reactive cells than H-2b mice. Surface staining of thymocytes indicates that in H-2b mice, T cell development is arrested at an intermediate stage of differentiation (CD4+8+, CD310). Analyses of mice carrying these T cell receptor genes and MHC class II I-E alpha constructs indicate that his developmental block can be reversed in H-2b mice by I-E expression on cortical epithelial cells of the thymus. These data suggest that a direct T cell receptor-MHC interaction occurs in the thymus in the absence of nominal antigen and results in the enhanced export of T cells, consistent with the concept of "positive selection".
Berg
L J
LJ
Department of Microbiology and Immunology, Stanford University School of Medicine, California 94305.
Pullen
A M
AM
Fazekas de St Groth
B
B
Mathis
D
D
Benoist
C
C
Davis
M M
MM
D000818:Animals; D000943:Antigens, Differentiation / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D018956:CD5 Antigens; D016827:CD8 Antigens; D005434:Flow Cytometry; D008024:Ligands; D008285:Major Histocompatibility Complex; D051379:Mice; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*
D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D018956:CD5 Antigens; D016827:CD8 Antigens; D008024:Ligands; D011948:Receptors, Antigen, T-Cell