Assignment of the gene coding for the T3-delta subunit of the T3-T-cell receptor complex to the long arm of human chromosome 11 and to mouse chromosome 9.

Recurring, site-specific chromosomal rearrangements are associated with several human syndromes and malignant disorders. Such nonrandom translocations involving chromosome 22 in band qil are numerous and found to be associated with a diversity ofneoplasms as well as constitutional disorders. Chromosome 11 in bands q23-q24 is similarly involved in several types of tumors as well as in a recurring constitutional reciprocal translocation with chromosome 22. Here we report the use of chromosomal in situ hybridization to compare the translocation breakpoints in the cytologically indistinguishable constitutional t(l1122) and the tumor-related t(l;22) associated with Ewing sarcoma and peripheral neuroepithelioma. We have shown that the breakpoints can be distinguished from each other with iespect to the locus encoding the constant region of the Ig A light chain (Co) at 22q11 and the ETSI locus at 1lq23--q24; ETSI has been called hu-ets-l or human cgets-l. The tumor-associated chromosome 11 breakpoint is also different from those of leukemias with t(9;11) and t(4;11) translocations, Southern-blot analysis showed no rearrangement ofETSI in these disorders in the region detected by our probe. ETSI has also been mapped more precisely to 11q23.3-+q24 by in situ hybridization to cells from an individual with an 11q23.3--qter deletion.Site-specific chromosome rearrangements are associated with both malignant and nonmalignant human disorders. Recurrent rearrangements involving chromosome 22 have been described both in the constitutional karyotype and as acquired somatic abnormalities in neoplastic diseases (1, 2). The breakpoints of the t(9;22) of chronic myelogenous leukemia, the t(9;22) of acute lymphocytic leukemia, and the t(8;22) of Burkitt lymphoma within 22q11 are cytologically indistinguishable. Chromosomal in situ hybridization has been used to map these translocation breakpoints more precisely and has shown that, in fact, the 22q11 breakpoints can be distinguished from each other at a molecular level (3,4).Recently, chromosome 22 has been shown to be involved in a reciprocal translocation with chromosome 11, t(11;22)-(q23-q24;qll-q12) in virtually all cases of swing sarcoma (ES) and peripheral neuroepithelioma (NE) examined cytogenetically (5-10). Askin tumor, a malignancy of the thoracopulmonary region, also has been found recently to have an apparently identical t(11;22) (10) and is likely a neuroepithelioma of the chest wall (11, 12). Recurrent rearrangements involving chromosome 11 at q23-q24 have also been reported in leukemias, including the t(4;11)(q21;q23) of acute lymphoblastic or undifferentiated leukemia (13) and the t(9;11)(q21;q23) of acute monocytic leukemia (14).The 11;22 rearrangement of ES, NE, and Askin tumor is cytologically indistinguishable from the recurrent constitutional chromosomal rearrangement that has been described (1), which involves the same chromosomal regions. The constitutional t(11;22)(q23;q11) is a site-specific, reciprocal translocation that has now been described in more ...

Section: Resultsmentioning

confidence: 99%

Comparison of constitutional and tumor-associated 11;22 translocations: nonidentical breakpoints on chromosomes 11 and 22.

Griffin¹,

McKeon²,

Israel³

et al. 1986

“…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.…”

Section: Discussionmentioning

confidence: 99%

“…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).…”

mentioning

confidence: 99%

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

Weissman¹,

Hou²,

Orloff³

et al. 1988

167

The T-cell antigen receptor (TCR) is a multisubunit receptor complex specific to T cells subserving both antigen recognition and signal transduction functions. The { chain of the TCR is a component of all surface receptor complexes. This chain was first identified in murine T cells by virtue of the fact that it coinmunoprecipitates with the TCR complex using antibodies directed against either the clonespecific subunits or invariant CD3 subunits of the receptor.Recently, we have isolated a cDNA encoding the murine C. Using this as a probe, we have now isolated cDNAs encoding the human {. Sequence analysis of cDNAs encoding human and murine { reveals that it is a highly conserved protein. In addition to amino acid homology, there is remarkable interspecies conservation in the nucleotide sequence of the 5' and 3' untranslated regions of the C mRNA. The previously characterized invariant 6, E, and y chains of the TCR, referred to as the CD3 complex, share significant sequence and structural homology with each other and are all located within 300 kilobases of each other on human chromosome 11 (11q23). Chas no sequence similarity to the CD3 chains and the localization of the human C gene to the centromeric region of chromosome 1 underscores the fact that it is a distinct genetic component of the TCR.Initiation of a normal immune response requires recognition of foreign antigen by T lymphocytes. This occurs when antigen-presenting cells bearing major histocompatibility complex (MHC) molecules bound with the appropriate antigen interact with T-cell receptors that recognize the MHCantigen complex as foreign. The T-cell antigen receptor (TCR) is a complex multisubunit structure whose components have been divided by both nomenclature and presumed function into two groups. The first group consists of the antigen recognition components of the receptor or Ti. On most T cells these components consist of a-j3 heterodimers, which are products of rearranged genes and are expressed in a clonally restricted manner (1-3). These clonotypic elements are immunoglobulin-like structures with constant and variable domains. The second group of receptor components are those that are constant in sequence for all T cells and are presumed to function primarily in signal transduction (4-11).The invariant 6, e, and y chains are collectively referred to as the CD3 complex. The members of the CD3 complex are related by amino acid sequence and are all members of the immunoglobulin gene superfamily (11-18). 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 (19-21).More recently, another invariant chain, ', has been discovered as part of the murine receptor complex (7). Although a (25,26). We have demonstrated that in human peripheral blood lymphocytes as in murine hybridomas this tyrosine kinase results in the tyrosine phosphorylation of ; with an increase in its apparent molecular mass from 16 to 21 kDa (27,...

“…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.…”

mentioning

confidence: 99%

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

Saito

Koyama

Georgopoulos

et al. 1987

Self Cite

Close linkage of the mouse and human CD3 v-and 6-chain genes suggests that their transcription is controlled by common regulatory elements (T-cell ABSTRACTAntigen receptors on the T-cell surface are noncovalently associated with at least four invariant polypeptide chains, CD3-'y, -8, -E, and -C. The mouse CD3-y gene, consisting of seven exons, was found to be highly homologous to the CD3-6 gene described earlier. Both the high level of sequence homology and the exon/intron organization indicate that the CD3-y and -8 genes arose by gene duplication.