The T cell receptor/CD3 complex: a dynamic protein ensemble.
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Amino Acid Sequence↗
Biomedical subjects
B Alarcon
Publications and source records attributed to B Alarcon.
T3-p28 is a protein associated with the delta and epsilon chains of the T cell receptor-T3 antigen complex during biosynthesis.
The human T cell receptor-T3 antigen complex is composed of at least five polypeptide chains. In addition to the 45-kDa/50-kDa heterodimer (alpha and beta chains) of the T cell receptor, the complex includes 25-kDa (T3-gamma) and 20-kDa (T3-delta) glycoproteins and a nonglycosylated 20-kDa (T3-epsilon) protein. Here we report that in pulse-chase biosynthetic labeling experiments we detect a new polypeptide chain (T3-p28) which is associated with the T3-delta and T3-epsilon chains during biosynthesis but not on the cell surface. T3-p28, which is not recognized by anti-T3 antibodies, can be chemically distinguished from the previously described T3-gamma chain. The carboxylic ionophore monensin blocks the apparent dissociation of T3-p28 from the T3-delta and T3-epsilon chains. Peripheral blood lymphocytes as well as all T cell leukemic lines tested contain T3-p28, except one HPB-ALL subline. Since the T3-p28 protein is only observed early in biosynthesis of T3-delta and T3-epsilon, it may function in intracellular transport or assembly of the T cell receptor-T3 complex.
Antigens, Surface↗
The T-cell receptor gamma chain-CD3 complex: implication in the cytotoxic activity of a CD3+ CD4- CD8- human natural killer clone.
A subset of human T cells has recently been described. These cells express the CD3 complex but they do not carry the classical T-cell receptor (TCR)-alpha/-beta heterodimer on their surface (WT31- CD3+). Instead, they express a TCR-gamma chain associated with another type of polypeptide termed TCR-delta. We report here that a T-cell clone with natural killer (NK)-like activity, WM-14, had a disulfide bridged TCR-gamma homodimer associated with CD3 on its surface. The TCR-gamma chains of WM-14 cells were present in three different glycosylation forms of 43, 40, and 38 kDa, but they appeared to contain the same polypeptide backbone. Since cytotoxicity by WM-14 could be inhibited by anti-CD3 antibodies, we concluded that the TCR-gamma-CD3 complex was involved in the NK-like unrestricted killer activity. Although normal CD3-gamma, CD3-delta, and CD3-epsilon chains were present in this clone, the association with the TCR-gamma homodimer may be the cause of a complete processing of the N-linked oligosaccharides attached to the CD3-delta chain.
Antibodies, Monoclonal↗
Evolutionary relationship between the T3 chains of the T-cell receptor complex and the immunoglobulin supergene family.
Antigen receptors on the surface of the thymus-derived (T) lymphocytes are associated with small integral membrane proteins called the T3 (CD3) gamma, delta, epsilon, and zeta chains. After interaction of the T-cell receptor with antigen, the T3 proteins are believed to transfer an activation signal to the intracellular compartment. In previous studies, the human gamma, epsilon, and delta chains have been cloned along with the mouse delta chain, but a relationship between these sequences and known molecular families has not been established. We now report the molecular cloning and characterization of the murine T3-epsilon protein and a sequence and structural analysis of the relationships between all the T3 chains and the immunoglobulin superfamily. It is established that the T3 chains are immunoglobulin-related and a particular relationship to the neural cell adhesion molecule (N-CAM) is noted. This sequence relationship adds interest to previous findings that the T3 chains are genetically linked to N-CAM and Thy-1 antigen on band q23 of human chromosome 11.
Animals↗
Antirhinovirus compound 44,081 R.P. inhibits virus uncoating.
44,081 R.P., or 2-[(1,5,10,10a-tetrahydro-3H-thiazolo[3,4-b]isoquinolin- 3-ylidine)amino]-4-thiazole acetic acid, is a compound which selectively inhibits rhinovirus in cell cultures. The compound, which was unable to inactivate infectivity of virions, appeared to act prior to RNA and protein synthesis without affecting adsorption or penetration of virus in MRC5 cells. In contrast, it protected intracellular [5-3H]uridine-labeled virions against the effects of RNase treatment, indicating that inhibition of virus uncoating is the mode of action of 44 081 R.P.
Adsorption↗
pppA2'p5A' blocks vesicular stomatitis virus replication in intact cells.
pppA2'p5'A blocked the production of infectious vesicular stomatitis virus in HeLa cells. When this compound was present from the beginning of infection, a selective inhibitory effect was observed in viral protein synthesis. Thus, cellular translation was not affected even after 10 h of incubation with this compound, and the bulk of viral proteins was not synthesized. However, this effect was not observed with ATP, GTP, or the core A2'p5'A. The step blocked by pppA2'p5'A is located early during virus infection, but adsorption, entry, and virus uncoating seemed to be unaffected by this compound. Analysis of the antiviral spectrum of pppA2'p5'A indicated that it is active against poliovirus, encephalomyocarditis virus, and Semliki Forest virus and shows no effect against herpes simplex virus type 1 and adenovirus type 5.
Adenine Nucleotides↗
Cellular vaccines.
This project is devoted to the development of novel cellular vaccines designed to treat cancer patients. These cellular vaccines present and enhance immunogens, which will elicit a potent immune response. The goal is to achieve safe and effective immune reaction against the patient's own tumour. (1) Autologous cellular vaccines are prepared by processing circulating blood mononuclear cells outside of the patient's body (ex vivo) to differentiate them into antigen-presenting cells (APCs). Monocyte-derived APCs (MD-APCs) are then grown in the presence of exogenous target antigens (tumour cell debris, or apoptotic bodies) to become fully mature APCs. (2) Functionality for antigen presentation to T cells of ex vivo MD-APCs is evaluated in vivo. (3) Cellular vaccines are tested in selected rodent animal models. Efficiency and immune response are monitored in pertinent experimental systems for cancer. Pharmacological data are generated for clinical investigation. Tolerance and biologic effects are documented in primates. (4) The first clinical trials on cancer patients are taking place in 1998 on melanoma and prostate cancer to validate the concept. Specialized cell processors with dedicated software and standardized controls are being developed and used for the preparation of cellular vaccines. (5) The evaluation of new non-viral vectors and the validation of new non-viral transfection methods of mononuclear cells with marker genes is in progress and will lead to the ex vivo transfection of genes coding for immunostimulating cytokines or for tumour antigens in MD-APCs. Efficiency will be validated in vitro and in animal models. The ex vivo and animal model studies validate the clinical relevance of this new cellular immunotechnology. Clinical validation of individual autologous cellular vaccines in specific indications for which no treatment is presently available will allow the development of cellular and gene immunotherapy for other types of cancers.
Animals↗