Rearrangement and expression of T cell antigen receptor and gamma genes during thymic development.

Abstract

Rearrangement and expression of the T cell antigen receptor and the gamma genes during T cell ontogeny is a regulated process; the gamma genes are rearranged and expressed first, followed by the beta and then the alpha genes. Expression of both functional alpha and beta gene RNA first occurs at day 17 of gestation, along with the expression of T3 delta chain RNA. T cell antigen receptor gene rearrangements occur primarily or exclusively in the thymus, although some gamma gene rearrangements occur outside the thymus in fetal liver cells that may be committed T cell progenitors. There is no gross difference in the extent of beta and gamma gene rearrangements in the adult thymocyte subpopulations that were analyzed, despite the fact that some of these populations cannot respond to antigen and never emigrate from the thymus. Quantitative analysis of rearrangements in total adult thymocyte DNA shows that beta gene rearrangements generally occur on both chromosomal homologs, and that rearrangements occur preferentially to the J beta 2 gene segment cluster.

T cell receptor alpha-, beta-, and gamma-genes in T cell and pre-B cell acute lymphoblastic leukemia.

“…Even the pre-B cells that rearranged both ,y TCR alleles retained one or both copies of the germline 12 T-ALLs reflect. This is consistent with a proposed murine sequence in which y expression precedes a, while ( is expressed throughout all of thymic development (33)(34)(35)(36). Curiously, the CTP T-ALLs usually have rearranged both y TCR alleles and have almost always utilized the C72 complex (Fig.…”

“…y TCR RNA decreased dramatically during intrathymic maturation, while (3 RNA remained constant, and a RNA increased (6,7,(33)(34)(35)(36). We sought to determine whether the T-ALLs represented a population of cells early enough in pre-T development to reveal any ordered usage of TCR genes in man.…”

Phenotypic Characterization of CD3−7+ Cells in Developing Human Intestine and an Analysis of Their Ability to Differentiate into T Cells

“…On a molecular level, TCR genes undergo sequentially ordered rearrangement during T cell differentiation. The rearrangement of the TCR ␥-genes precedes that of ␤-and ␣-chain genes and is one of the earliest signs of T cell lineage commitment common to all T cells (35,36). We were able to detect rearranged TCR ␥-chains in the CD3 Ϫ 7 ϩ cells in human fetal and adult gut indicating that a proportion of CD3…”

T cell receptor alpha-chain gene rearrangements in B-precursor leukemia are in contrast to the findings in T cell acute lymphoblastic leukemia. Comparative study of T cell receptor gene rearrangement in childhood leukemia.

“…n-Chain gene rearrangement and expression are the first events in T cell ontogeny, followed by 3-chain gene rearrangement and expression. a-Chain gene expression is observed only in mature thymocytes and peripheral T cells which have T3 antigen on the cell surface (19,(23)(24)(25)(26)(27)(28). In view ofthis, it has been proposed that a-chain gene rearrangements may be regulated by a product ofthe rearranged ,8-chain gene, and this specific event would be restricted to cells of T lineage.…”

“…After analysis ofthe findings of TCR gene configuration, the 46 patients with B-precursor ALL were tentatively divided into five subgroups as shown in Table II with B-precursor ALL showed a combination of TCR gene rearrangements consistent with the proposed hierarchy that -y-chain gene rearrangement is the first event followed by fchain rearrangement and subsequently a-chain gene rearrangement (19,(23)(24)(25)(26)(27)(28) these data have provided insights into the differentiation process of hematopoietic cells (3)(4)(5)(6)(7)(8)(9)(10)(11)(40)(41)(42).…”