Engagement of the T-cell receptor during positive selection in the thymus down-regulates RAG-1 expression.
We have examined the expression of the recombination activating gene RAG-1 by in situ hybridization to thymi from mice bearing transgenes for the T-cell receptor (TCR) alpha chain, TCR beta chain, or both TCR alpha and beta chains. RAG-1 transcription was found in the thymic cortex of transgenic mice carrying a single TCR alpha- or TCR beta-chain transgene, comparable to normal mice. However, RAG-1 transcription was strikingly reduced in the thymic cortex from transgenic mice carrying both TCR alpha- and beta-chain genes and expressing major histocompatibility complex (MHC) class I (H-2b) molecules necessary for positive selection of the transgenic TCR. In contrast, thymi of transgenic mice also carrying both TCR alpha- and beta-chain genes but expressing MHC molecules (H-2d) that did not positively select the transgenic TCR displayed high levels of RAG-1 transcription. The low thymic RAG-1 expression coincided with high transgenic TCR alpha-chain surface expression and with inhibition of endogenous TCR alpha-chain rearrangement. Our findings suggest that binding of the TCR to self MHC molecules during positive selection down-regulates RAG-1 transcription in cortical thymocytes and thereby prevents further TCR alpha-chain rearrangements.
Brändle
D
D
Institute of Experimental Immunology, University of Zurich, Switzerland.
Müller
C
C
Rülicke
T
T
Hengartner
H
H
Pircher
H
H
D000818:Animals; D001483:Base Sequence; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D002454:Cell Differentiation; D002462:Cell Membrane / Q000378:metabolism; D015870:Gene Expression; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D018398:Homeodomain Proteins; D017403:In Situ Hybridization; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology / Q000502:physiology*; D013950:Thymus Gland / Q000502:physiology
D015704:CD4 Antigens; D016827:CD8 Antigens; D018398:Homeodomain Proteins; D009838:Oligodeoxyribonucleotides; D011506:Proteins; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta; C064658:RAG-1 protein