Selection of amino acid sequences in the beta chain of the T cell antigen receptor

The induction of an immune response in mammals is initiated by specifically reactive T lymphocytes. The specificity of the reaction is mediated by a complex receptor, part of which is highly variable in sequence and analogous to immunoglobulin heavy- and light-chain variable domains. The functional specificity of the T cell antigen receptor is, however, markedly different from immunoglobulins in that it mediates cell-cell interactions via the simultaneous recognition of foreign antigens and major histocompatibility complex-encoded molecules expressed on the surface of various lymphoid and nonlymphoid cells. The relation between the structure of the receptor and its functional specificity was investigated by analyzing the primary sequences of the receptors expressed by a series of T lymphocyte clones specific for a model antigen, pigeon cytochrome c. Within this set of T lymphocyte clones there was a striking selection for amino acid sequences in the receptor beta-chain in the region analogous to the third complementarity-determining region of immunoglobulins. Thus, despite the functional differences between T cell antigen receptors and immunoglobulin molecules, analogous regions appear to be important in determining ligand specificity.     

A novel mechanism of somatic rearrangement predicted by a human T-cell antigen receptor beta-chain complementary DNA

The T-cell antigen receptor is a cell surface molecule vital in mediating the cellular immune response. The arrangement and rearrangement of the gene segments encoding the beta-chain polypeptide of the receptor are similar to those of immunoglobulin gene segments. The two constant region genes of the human T-cell antigen receptor are 8 kilobases apart with a cluster of joining segments located 5' of each constant region gene. Although most beta-chain gene rearrangements involve the variable, diversity, and joining segments, analysis of a beta-chain complementary DNA clone suggests the occasional occurrence of another type of rearrangement.     

Location of gene for beta subunit of human T-cell receptor at band 7q35, a region prone to rearrangements in T cells

The T-cell receptor is formed by two chains, alpha and beta, for which specific clones were recently obtained. In this report the gene for the beta chain of the human T-cell receptor was located on the long arm of chromosome 7, band q35, by means of in situ hybridization. This chromosome region in T cells is unusually prone to develop breaks in vivo, perhaps reflecting instability generated by somatic rearrangement of T-cell receptor genes during normal differentiation in this cell lineage.     

Chromosomal location of human T-cell receptor gene Ti beta

A complementary DNA probe corresponding to the beta-chain gene of Ti, the human T lymphocyte receptor, has been molecularly cloned. The chromosomal origin of the Ti beta gene was determined with the complementary DNA by screening a series of 12 cell hybrid (mouse X human) DNA's containing overlapping subsets of human chromosomes. DNA hybridization (Southern) experiments showed that the human Ti beta gene resides on chromosome 7 and is thus not linked to the immunoglobulin loci or to the major histocompatibility locus in humans.     

Interleukin-2 receptor beta chain gene: generation of three receptor forms by cloned human alpha and beta chain cDNA's

Interleukin-2 (IL-2) binds to two distinct receptor molecules, the IL-2 receptor alpha (IL-2R alpha, p55) chain and the newly identified IL-2 receptor beta (IL-2R beta, p70-75) chain. The cDNA encoding the human IL-2R beta chain has now been isolated. The overall primary structure of the IL-2R beta chain shows no apparent homology to other known receptors. Unlike the IL-2R alpha chain, the IL-2R beta chain has a large cytoplasmic region in which a functional domain (or domains) mediating an intracellular signal transduction pathway (or pathways) may be embodied. The cDNA-encoded beta chain binds and internalizes IL-2 when expressed on T lymphoid cells but not fibroblast cells. Furthermore, the cDNA gives rise to the generation of high-affinity IL-2 receptor when co-expressed with the IL-2R alpha chain cDNA.     

猪T细胞受体β链基因的克隆及生物信息学分析

以GenBank上登载的猪的T细胞受体β(pTCR-β)基因为参考序列,用RT-PCR法从猪的外周血淋巴细胞中克隆了TCR-β链基因,并进行生物信息学分析.结果表明:pTCR-β基因含有一个完整的开放阅读框架(ORF),大小为849bp,编码283个氨基酸,且含有一段27个氨基酸的信号肽序列,与参考序列相比,在核苷酸序列上的同源性为80.4%,在氨基酸序列上的同源性为70.3%;生物信息学结构预测发现2个结构域,一个为IG结构域,由第32-138位共107个氨基酸残基组成;另一个为IG-LIKE结构域,由第164-211位共48个氨基酸残基组成.     

Molecular cloning of the zeta chain of the T cell antigen receptor

The T cell antigen receptor is a multi-subunit receptor complex present on the surface of all mature and many developing T cells. It consists of clonotypic heterodimers noncovalently linked to five invariant chains that are encoded by four genes and referred to as the CD3 complex. The CD3 gamma, delta, and epsilon chains have been molecularly characterized. In this report the molecular cloning of a complementary DNA encoding the zeta chain of the murine T cell antigen receptor is described. The predicted protein sequence of the zeta chain suggests a structure distinct from those of any of the previously described receptor subunits.     

Novel viral sequences related to human T-cell leukemia virus in T cells of a seropositive baboon

Antibodies reactive with proteins of human T-cell leukemia virus (HTLV) can be found in Old World monkeys. A T-lymphocyte cell line established from a seropositive baboon (Papio cynocephalus) was analyzed for the presence of viral DNA sequences. The provirus found in these cells was related to but distinct from HTLV subgroup I. These results add to recent evidence from human studies that HTLV represents a spectrum of infectious T-lymphotropic retroviruses that includes closely and distantly related members.     

Selective depletion in HIV infection of T cells that bear specific T cell receptor V beta sequences

The mechanism of T cell depletion during infection with the human immunodeficiency virus (HIV) is unclear. Examination of the repertoire of T cell receptor V (variable) regions in persons infected with HIV revealed the absence of a common set of V beta regions, whereas V alpha usage was normal. The lack of these V beta segments did not appear to correlate with opportunistic infections. The selective elimination of T cells that express a defined set of V beta sequences may indicate the presence of an HIV-encoded superantigen, similar to those encoded by the long terminal repeat of the mouse mammary tumor virus.     

Intracellular accumulation of T-cell receptor complex molecules in a human T-cell line

This work was aimed at understanding the mechanisms of T-lymphocyte function by studying the cellular distribution and traffic of molecules of the T-cell receptor complex. The accumulation of specific molecules in intracytoplasmic vesicles is related to the activation of T lymphocytes. Some of these molecules include acid hydrolases, the transferrin receptor, and class I antigens of the major histocompatibility complex. Molecules of the T-cell receptor complex have now also been found in intracytoplasmic vesicles in a human T-cell line derived from a lymphoblastic leukemia. Such vesicles were tightly associated with the cytoplasmic microtubule network. One functional aspect of this association is a cellular pathway by which vesicles traveling to and from the cell surface converge in an area of the cells that is rich in processing enzymes.     

Gene for alpha-chain of human T-cell receptor: location on chromosome 14 region involved in T-cell neoplasms

A human complementary DNA clone specific for the alpha-chain of the T-cell receptor and a panel of rodent X human somatic cell hybrids were used to map the alpha-chain gene to human chromosome 14 in a region proximal to the immunoglobulin heavy chain locus. Analysis by means of in situ hybridization of human metaphase chromosomes served to further localize the alpha-chain gene to region 14q11q12, which is consistently involved in translocations and inversions detectable in human T-cell leukemias and lymphomas. Thus, the locus for the alpha-chain T-cell receptor may participate in oncogene activation in T-cell tumors.     

Functional properties of antigen-specific T cells infected by human T-cell leukemia-lymphoma virus (HTLV-I)

Tetanus-toxoid specific helper-inducer T-cell clones, which had been infected and transformed by human T-cell leukemia-lymphoma virus (HTLV-I), were obtained from an antigen-specific human T cell line by using a limiting dilution technique in the presence of the virus. These HTLV-I-infected T-cell clones proliferated specifically in response to soluble tetanus toxoid but, unlike normal T cells, they could do so in the absence of accessory cells. The HTLV-I-infected T-cell clones did not present the antigen to autologous antigen-specific T cells that were not infected with HTLV-I. The capacity of helper-inducer T cells to retain antigen-specific reactivity after infection by HTLV-I, while losing the normal T-cell requirement for accessory cells, has clinical and theoretical implications.     

Antibodies to hepatitis B surface antigen potentiate the response of human T lymphocyte clones to the same antigen

Human t-helper lymphocyte clones specific for hepatitis B virus surface antigen (HBsAg) proliferate on stimulation with HBsAg in vitro. Antibodies specific for HBsAg, but no other antibodies, augment this proliferative response. In the presence of antibodies to HBsAg, the maximum response could be achieved at HBsAg concentrations that were 1 percent of those required in the absence of the antibodies. These findings suggest that antigen-specific antibodies exert regulatory controls on T cells that recognize the same antigens.     

CAR-T细胞免疫疗法在肿瘤治疗中的研究进展

嵌合抗原受体T细胞免疫疗法(chimeric antigen receptor therapy,CAR-T)作为一种肿瘤免疫治疗方法,具有良好的治疗前景.该文总结了CAR-T细胞治疗的发展历程与临床研究进展,阐述了CAR-T细胞治疗耐药机制,并提出了优化CAR-T细胞治疗的策略.     

T-cell growth factor gene: lack of expression in human T-cell leukemia-lymphoma virus-infected cells

Activated mature T cells require T-cell growth factor (TCGF) for continuous proliferation. However, many mature T cells infected with human T-cell leukemia-lymphoma virus grow independently of exogenously added TCGF. It is now reported that cells infected with this virus also lack detectable TCGF messenger RNA (less than one copy per cell) and thus do not produce their own growth factor. The results apparently rule out an autostimulation mechanism of growth control.     

Structural mutations of the T cell receptor zeta chain and its role in T cell activation

T cell hybridomas that express zeta zeta, but not zeta eta, dimers in their T cell receptors (TCRs) produce interleukin-2 (IL-2) and undergo an inhibition of spontaneous growth when activated by antigen, antibodies to the receptor, or antibodies to Thy-1. Hybridomas without zeta and eta were reconstituted with mutated zeta chains. Cytoplasmic truncations of up to 40% of the zeta molecule reconstituted normal surface assembly of TCRs, but antigen-induced IL-2 secretion and growth inhibition were lost. In contrast, cross-linking antibodies to the TCR activated these cells. A point mutation conferred the same signaling phenotype as did the truncations and caused defective antigen-induced tyrosine kinase activation. Thus zeta allows the binding of antigen/major histocompatibility complex (MHC) to alpha beta to effect TCR signaling.