Two tandemly organized human genes encoding the T-cell γ constant-region sequences show multiple rearrangement in different T-cell types

Abstract

The recent detailed analysis of genes that undergo rearrangement in T cells has shown that the T-cell receptor genes encoding alpha- and beta-chains are involved in specific alterations in T-cell DNA analogous to the immunoglobulin genes. A third type of gene, designated gamma, has been isolated from mouse cytotoxic T lymphocytes, and evidence suggest that the mouse displays very limited diversity in this gene system, having only three variable-region (V) genes and three constant-region (C) genes. The function of the so-called T-cell gamma gene is unknown. We have isolated genomic genes encoding the human homologue of the mouse T-cell gamma gene; as there is no evidence that this T-cell rearranging gene is anything to do with the T3 molecule, we have designated the human T-cell rearranging gene as TRG gamma (ref. 13), to avoid confusion with the T3 gamma-chain, and have shown that the gene locus maps to chromosome 7 in humans. We now report that human DNA contains two tandemly arranged TRG gamma constant-region genes about 16 kilobases apart. These two genes show multiple rearrangement patterns in a variety of T cells, including helper and cytotoxic/suppressor type, as well as in all forms of T-cell leukaemia. Our results indicate variability of this T-cell gene system in man compared with the analogous system in mouse.

CD56+ CD7+ Stem Cell Leukemia/Lymphoma with D2-J.DELTA.1 Rearrangement.

“…The monoclonal antibodies (MoAbs) used were as follows: CD1 (recognized by T6), CD2 (Til), CD3 (Leu 4), CD4 (T4), CDS (Leu 1), CD7 (3A1), CD8 (T8). CD19 (Leu 12 and/or B4) and CD20 (Bl) were used for B-cell markers; CD13 (My 7) and CD33 (My9) as early myeloid markers; and CD34 (25). The rearrangements of the TCRychain gene were examined by using a 1.0 Kb germline Pstl-EcoRI fragment containing the first J8 region (J8l), a 1.5 Kb Xbal genomic fragment containing the third J8 region (J83), the D8l/ 2 genomic fragment, a 2.6 Kb EcoRI-EcoRI, and a 1.5 Kb CS region probe isolated from a thymic complementary DNA (CDNA) clone including the 3' -untranslated region (26,27).…”

Rearrangements to the JP1, JP and JP2 segments in the human T‐cell rearranging gamma gene (TRGγ) locus

“…The JT probe, pH60, containing the 700 base pair (bp) HindIII-EcoRI from M13H60 [1] subcloned in pUC9, includes the Jyl segment [7], this Jyl probe cross-hybridizing with J'r2 but not with the additional Jy segments. The VyI probe, 1.1 kilobase (kb) SacI Vy3 fragment from ASH4 [10], detects the nine Vy genes belonging to subgroup I [11].…”

“…In unrearranged clones these additional J segments are localized in a 2.4 kb and a 1.1 kb EcoRI fragment located respectively upstream of those containing JP and J2 [9]. A 2.4 kb EcoRI fragment containing the JP1 segment was obtained from ARy, a clone isolated from a phage library of the Burkitt's lymphoma cell line Raji [1]. HindIII-EcoRI subclones were sequenced from the HindIII site.…”

“…The human T-cell rearranging 7 gene (TRG7) has been identified [1,2] by homology with a mouse gene that has been shown to undergo rearrangement specifically in T-cells [3,4]. Human TRG7 genes have been mapped to chromosome 7 [5] at band 7p15 [2].…”

“…The TRG7 locus like other studied rearranging genes has variable (V) region genes, joining (J) and constant (C) region segments which join during the early stage of T-cell differentiation [6]. Two human constant-region genes have been identified [1,[7][8][9] which are linked to each other at 16 kilobases [1,9]. 14 variable 7 genes belonging to four subgroups [7,10,11] are located upstream of the two C7 genes (fig.lA).…”