The gene encoding the epsilon subunit of the T3/T-cell receptor complex maps to chromosome 11 in humans and to chromosome 9 in mice.

Abstract

The T3 complex is composed of three polypeptide chains that are both structurally and functionally associated with the receptor for antigen on the surface of human T lymphocytes. In a series of experiments utilizing both somatic cell hybrids and chromosomal hybridization in situ, the genes encoding two members of the human T3 complex, T3-6 and T3-e, were found to reside on the long arm of chromosome 11 in band q23. The murine T3-e gene was localized to chromosome 9. The location of the T3-6i and T3-E genes with respect to the Hu-ets-l gene, which is also located in 11q23, is discussed. Recent assignments of several genes, preferentially expressed in human cells of hematopoietic and neuroectodermal origins, to band q23 of human chromosome 11 and the murine equivalents to murine chromosome 9 may defre a conserved gene cluster important in cell proliferation and differentiation.T lymphocytes recognize foreign antigens in association with molecules of the major histocompatibility complex (MHC) via a complex composed of at least five membrane proteins, the so called T3/T-cell receptor complex (1-3). Earlier, we hypothesized that, after recognition of foreign antigen by the a and , chains of the disulfide-linked heterodimeric T-cell antigen receptor, signal transduction of the recognition event occurs via the three T3 polypeptide chains, y, 8, and E (4).The genes encoding the a and ,B chains in both humans and mice have been cloned (5-8) and shown to be genetically unlinked (9-12) members of the immunoglobulin supergene family (reviewed in ref. 13). Recently, we have published our findings on the cDNA and genomic cloning of the human and murine T3-8 chain (14-16) and the cDNA cloning of the human T3-E chain (17). In an analysis of the amino acid sequence of the T3-3 and T3-E proteins predicted from their cDNA sequences, we noted that a partial structural homology existed that might account for the association of these two chains with the T-cell receptor heterodimer (17). Previously we assigned the human T3-8 gene to the long arm of chromosome 11 in the region llq23--qter and the murine equivalent to chromosome 9 (18). Hence, we were interested in defining the location of the T3-E gene to determine whether these two genes, T3-5 and T3-e, whose protein products are members of a functional complex, would be associated in the genome. The present study shows that the human T3-e gene is also found on human chromosome 11 and the murine equivalent is on murine chromosome 9. Further, as determined by chromosomal in situ hybridization studies, we show that the genes coding for both human T3-5 and T3-E are located in band 11q23, a region known to contain several genes believed to be important in proliferation and differentiation of cells of hematopoietic and neuroectodermal origins (19-24). MATERIALS AND METHODSSomatic Cell Hybrids. DNA from three panels of humanrodent somatic cell hybrids was used to determine the segregation of the human T3-E gene. The first two panels were derived from the fusion of the hypoxanthine p...

Molecular cloning and chromosomal localization of the human T-cell receptor zeta chain: distinction from the molecular CD3 complex.

“…That ; is localized to chromosome 1 is of particular interest given that all the other invariant receptor components are not only colocalized to chromosome 11 but are present within 300 kb of each other (19)(20)(21). Near CD3 on chromosome 11 are other members of the immunoglobulin gene superfamily including Thy-1 and NCAM.…”

“…In addition, the CD3 components are all clustered within 300 kilobases (kb) of each other on human chromosome 11q23. The genes for the CD3 6 and y reside within 1.6 kb of each other (19)(20)(21).…”

Possible association of CD3 and CD4 polymorphisms with insulin-dependent diabetes mellitus (IDDM)

“…Since CD4 and CD3 are encoded by genes located on chromosome 12p [23] and Ilq23 [8,24], respectively, and the HLA class II genes are located on chromosome 6p [25], they are inherited independently of each other. Our results therefore tentatively suggest that CD4 and CD3 genes or linked genes might contribute independently of each other to an increased or decreased susceptibility of particular individuals to develop IDDM.…”

“…The Thy-I locus encoding the Thy-I glycoprotein, belonging to the immunoglobulin supcrfamily proteins, expressed in the brain and in the immune system, is tightly linked to human chromosome Ilq23 [7]. The CD3 complex {^(,h,f) is also encoded within a 60-kb stretch of DNA on human chromosome I Iq23; the CD3^ and 7 genes are located 26 kb upstream ofthe CD3e gene [7,8].…”

Close linkage of the mouse and human CD3 gamma- and delta-chain genes suggests that their transcription is controlled by common regulatory elements.

“…Previous work (13,14) showed that the CD3-8 and -E genes map close to each other on human chromosome 11 (band q23) and on mouse chromosome 9. The data presented here demonstrate that the three members of the CD3 gene family map to the same chromosome in humans and mice and that the CD3-y gene is (16) is indicated.…”