Binding of thymic factors to the conserved decanucleotide promoter element of the T-cell receptor V beta gene is developmentally regulated and is absent in SCID mice.
The gene segments encoding the beta chain of the T-cell antigen receptor undergo rearrangement in a precise developmental order: a D beta gene segment joins to a J beta gene segment prior to the rearrangement of a V beta gene segment to join the D/J beta fusion. Current evidence suggests that the rearrangement of V beta is restricted to T cells, whereas D-to-J beta rearrangements may occur in both B and T cells. Thus, the T-cell specificity seems to be regulated by the V beta coding region or its 5' flanking sequence. In support of this hypothesis, evidence is provided for thymus-specific factors that bind a highly conserved 10-base-pair (decamer) sequence that is an essential promoter element in mouse and human V beta genes. The presence of decamer-binding activities was assayed by gel mobility-shift analysis using protein extracts from thymus, spleen, and nonlymphoid organs of adult mice. Two shifted complexes, designated T2 and T3, were seen only when the decamer was incubated with extracts from thymus. When extracts from mice of various gestational ages were tested for decamer-binding activity, one of the thymus-specific complexes, T2, was first detected at day 16; this coincides with the time of initial activation of the V beta locus. No decamer-binding activity was detected in extracts prepared from the thymuses of SCID (severe combined immunodeficiency) mice, which characteristically fail to rearrange these genes. Moreover, neither T2 nor T3 was detectable with extracts from spleen or from two T-cell lines that express the beta chain; this suggests that the presence of these two complexes is not absolutely required for transcription of the T-cell receptor beta locus. We conclude that there are tissue-specific and developmentally regulated factors that form complexes with the decamer sequence 5' of V beta; these may represent initiation factors that control the activation of germ-line T-cell receptor V beta genes for transcription and/or rearrangement.
Lanier
E R
ER
Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio 78284-7762.
Brown
R M
RM
Kraig
E
E
D000367:Age Factors; D000818:Animals; D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000378:metabolism; D007153:Immunologic Deficiency Syndromes / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D016693:Receptors, Antigen, T-Cell, alpha-beta; D013949:Thymus Extracts / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology / Q000196:embryology / Q000502:physiology*
D004268:DNA-Binding Proteins; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D013949:Thymus Extracts