Evidence for the T3-associated 90K heterodimer as the T-cell antigen receptor

Meuer, Stefan; Acuto, Oreste; Hussey, Rebecca E.; Hodgdon, James C.; Fitzgerald, Kathleen A.; Schlossman, Stuart F.; Reinherz, Ellis L.

doi:10.1038/303808a0

Cited by 493 publications

(243 citation statements)

References 17 publications

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“…Biochemically, the clonotypic receptor consists of two disulphide-linked chains, a basic β chain and an acidic α chain, both of which have a molecular weight between 40 and 50 kd [33][34][35]. By peptide mapping, these chains differ from each other and appear to have variable and constant sequence properties [34,36].…”

Section: The T-cell Receptor For Antigen and Mhc Proteinsmentioning

confidence: 99%

A synaptic basis for T-lymphocyte activation

Norcross

1984

Annales de l'Institut Pasteur / Immunologie

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SummaryT lymphocytes respond to foreign antigen by forming specialized junctions with antigen-presenting cells (APC) or target cells. A hypothesis is presented, illustrating the similarity between the T-cell recognition-activation process and the cell communication processes found in other organ systems, especially the nervous system. Based on data showing that a major neuronal protein, Thy-1, is also a mitogenic site on T cells, and based on predictions for the structures of the T-cell receptor (TcR) and Ia proteins, an activation model is presented as follows. 1) The T-cell receptor initiates cell-cell contact with the APC by interacting with Ia and antigen, forming an antigen-binding site. 2) Sets of adhesion molecules then bind, focusing the interacting proteins to the junctional site. One binding protein, L3/T4, binds Ia and concentrates the Ia molecules to the contact site.3) The two-chain TcR then links together the TcR-Ia-antigen complexes, forming a linear chain of receptors which will self-associate once reaching a critical length, forming a cluster. This cluster juxtaposes associated channel subunits, the T3 membrane molecules, creating an ion channel, stimulating the T cell. 4) The MHC molecule is structurally a part of this activation complex, and therefore also forms a cluster on the APC surface, possibly activating the presenting cell. 5) Secretory products are then released into the synaptic site allowing for efficient and directed cell-cell communication. Cytolytic class-Irestricted cells use a similar pathway to focus the effect of cytolytic proteins.This analogy views neuronal communication and lymphoid recognition as evolutionary descendents of a primordial lymphocytic type of cell interaction.

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Section: The T-cell Receptor For Antigen and Mhc Proteinsmentioning

confidence: 99%

A synaptic basis for T-lymphocyte activation

Norcross

1984

Annales de l'Institut Pasteur / Immunologie

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“…Most nature, CD3-bearing peripheral blood T cells have a heterodimeric T-cell antigen receptor (TCR) composed of a and ,B chains (1)(2)(3)(4). However, T cells appearing early in thymic ontogeny and dendritic epidermal cells display an alternative heterodimeric TCR, consisting of y and 8 chains, in association with the CD3 molecule (5)(6)(7)(8).…”

mentioning

confidence: 99%

Human T-cell antigen receptor (TCR) delta-chain locus and elements responsible for its deletion are within the TCR alpha-chain locus.

Hockett

Villartay

Pollock

et al. 1988

Proc. Natl. Acad. Sci. U.S.A.

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Individual T cells express the CD3 molecule in association with alternative y8 or ad heterodimeric T-cell receptors (TCRs). T-cell precursors and occasional y8-expressing T cells in humans possess an unexpected 2.0-kilobase (kb) mRNA in which a tandemly repeated motif, TEA (T early a), has been spliced to the constant (Ca) region. Long-range pulsed-field gel mapping as well as molecular cloning showed that TEA is located immediately 5' to the most upstream joining (J.) segment of the TCR a-chain locus. The TCR 8-chain locus is immediately 5' to TEA, and diversity (Dt,) Ds]-Ds2-J1-Cs,-TEA was deleted in mature, an-expressing T cells, whereas Vtl was frequently retained. The location of the 6 locus within the a locus may necessitate an exclusive choice between 8 or a expression.Most nature, CD3-bearing peripheral blood T cells have a heterodimeric T-cell antigen receptor (TCR) composed of a and ,B chains (1-4). However, T cells appearing early in thymic ontogeny and dendritic epidermal cells display an alternative heterodimeric TCR, consisting of y and 8 chains, in association with the CD3 molecule (5-8). Much is known about the genes encoding the a, P, and y chains, and their TCR products are derived from somatic recombination of variable (V), joining (J), and at times diversity (D) gene segments upstream of the constant-region (C) genes found in these loci (9). Recently, cDNA clones encoding the murine and human 8 subunits have been characterized and aspects of the murine 8 genomic region have been elucidated (10-15). To understand the recombination of the human 8 locus, we characterized the genomic locus and examined T-cell-type acute lymphoblastic leukemias (ALLs) as monoclonal expansions of cells at serial stages of thymic development (16).We previously described a 2.0-kilobase (kb) mRNA that contains C, sequence and is expressed predominantly in early fetal thymocytes (17

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“…This direct mitogenic action is only found at high antibody cell ratlos it has practicaliy vamshed already at the fourfold higher dilution of 9 3 mAb (Table 4) whtre is thc enhancemeni of growth piomoting Signals is deteeted even at η g/ml 9 3 mAb [5] It may be concluded that the mitogenic action of 9 3 mAb depends on the prestnee of monocytes and is quenched by HS Α likely cause of the suppression of the mitogenic action in media supplemcnted by HS is their relativcly high content in human immunoglobulm molecules It might then be proposed that the binding of 9 3 mAb to Fc reeeptors of monocytes and as a consequence the possibie clustering of 190/44 is function dlly important This hypothesis is further supported by the recently reported finding that F(ab) 2 but not l· h fragments of 9 3 mAb have functional tffects on Γ cclls [17] Howevtr it cannot be exeluded that the quenching by IIS is at least in part due to thc presence of matenal which reacts with 9 3 mAb (e g shed T90/44) [5] 3.5 Γ90/44 expression is mduced in activated Γ cells…”

Section: Lymphocyte Transformation Testsmentioning

confidence: 77%

T90/44 (9.3 antigen). A cell surface molecule with a function in human T cell activation

et al. 1986

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T90/44 is a cell surface antigen which is present on human T cells of the helper and cytotoxic subsets and which binds the 9.3 monoclonal antibody (9.3 mAb). It is expressed in the form of 90‐kDa disulfide‐bonded dimers of a 44‐kDa polypeptide and of free 44‐kDa subunits. The function of T90/44 was investigated in a series of T cell function assays. 9.3 mAb was found to inhibit the activation of class II‐restricted cloned T helper cells derived from leprosy patients and reactive with M. leprae antigens. The inhibition was first found at 1–10 ng/ml 9.3 mAb and regularly increased with the antibody concentration. The extent of the inhibition varied among different T cell clones in proportion to the respective different levels of T90/44 expression at their cell surface. The proliferative responses of peripheral blood lymphocytes (PBL) to purified protein derivative of M. tuberculosis (PPD) and tetanus toxoid were enhanced by the 9.3 mAb resulting in up to 20–30‐fold increase of [3H]‐thymidine incorporation. After phytohemagglutinin‐induced activation of PBL, the number of T90/44 molecules per cell expressed at the cell surface rose from day 0 to day 7 by a factor of about 10. High concentrations of 9.3 mAb (5–10 μ/ml) at low cell densities and in the presence of monocytes in culture media supplemented by fetal calf serum were directly mitogenic for resting lymphocytes. The cytolytic effector functions of class I‐restricted cytotoxic T lymphocytes (CTL) were not modulated by 9.3 mAb. The mixed lymphocyte reactions of three class I‐restricted CTL to their specific target cells were found not to be significantly influenced bv 9.3 mAb. In conclusion it is proposed that an antigen‐independent T cell activation pathway can be entered at T90/44.

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Evidence for the T3-associated 90K heterodimer as the T-cell antigen receptor

Cited by 493 publications

References 17 publications

A synaptic basis for T-lymphocyte activation

A synaptic basis for T-lymphocyte activation

Human T-cell antigen receptor (TCR) delta-chain locus and elements responsible for its deletion are within the TCR alpha-chain locus.

T90/44 (9.3 antigen). A cell surface molecule with a function in human T cell activation

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