T-cell-specific deletion of T-cell receptor transgenes allows functional rearrangement of endogenous alpha- and beta-genes.
In B cells the loci encoding immunoglobulin chains usually show allelic exclusion; a given B cell transcribes and translates only one productively rearranged allele of the heavy and light chain loci. This ensures that each B cell expresses only one antigen receptor. The loci encoding T-cell receptor (TCR) alpha- and beta-genes may behave similarly. We have previously reported that the expression of a transgenic TCR beta-chain prevents functional and nonfunctional V beta rearrangements in the endogenous beta-chain loci but not D beta J beta rearrangements. We have also been unable to detect the expression of the TCR gamma-chain locus in thymocytes of these mice (unpublished observations). To study the mechanisms involved in forming a mature T-cell repertoire further, we have constructed mice expressing alpha- and beta-TCR transgenes derived from a cytotoxic T-cell clone that is specific for the male antigen H-Y in the context of H-2Db MHC molecules. Here we show that in these mice rearrangement of endogenous alpha-chain loci is also suppressed, although to a lesser extent than rearrangement of beta-chain loci. In addition, in male alpha beta TCR transgenic mice we observed T-cell clones which had deleted both transgenic alpha- and beta-chain genes and expressed endogenous alpha- and beta-chain TCR genes. These cells are presumably derived from rare thymocytes that leave the male thymus because their TCR no longer recognizes self antigen. The vast majority of CD4+8+ nonmature thymocytes expressing alpha- and beta-transgenes are deleted in the male thymus.
Blüthmann
H
H
Central Research Unit, F. Hoffmann-La Roche & Co. Ltd, Basel, Switzerland.
Kisielow
P
P
Uematsu
Y
Y
Malissen
M
M
Krimpenfort
P
P
Berns
A
A
von Boehmer
H
H
Steinmetz
M
M
D000818:Animals; D002872:Chromosome Deletion; D003602:Cytotoxicity, Immunologic; D005260:Female; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D008822:Mice, Transgenic / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D011995:Recombination, Genetic; D013601:T-Lymphocytes / Q000145:classification / Q000502:physiology*; D014018:Tissue Distribution; D014158:Transcription, Genetic
D011948:Receptors, Antigen, T-Cell