Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “CD3 Complex”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 109 records · Page 6Linked to original sources
PubMed1989

The CD2 antigen associates with the T-cell antigen receptor CD3 antigen complex on the surface of human T lymphocytes.

T lymphocytes can be activated by various stimuli directed either against the T-cell antigen receptor-CD3 antigen complex (Ti-CD3) or the CD2 molecule; see ref. 1 for a review. Activation signals generated by antigen binding to the antigen-specific alpha/beta heterodimer (Ti) are thought to be transduced via the invariant CD3 gamma, epsilon and delta chains, and the associated zeta and eta subunits. The physiological role of the interaction of CD2 with its homologous cell-surface associated ligand LFA-3 remains to be fully elucidated. It has been suggested that CD2 regulates an antigen-independent pathway of activation or that signals delivered via CD2 are an integral part of the antigen-specific pathway. Several recent studies have indicated a requirement for the Ti-CD3 complex in CD2 signalling. Thus, mutant T-cell lines expressing CD2, but not Ti-CD3, on the cell surface cannot be activated via the CD2 molecules. Functional interaction between the Ti-CD3 complex and the CD2 antigen suggests that these T-lymphocyte cell-surface structures are physically associated. Here we use a digitonin-based solubilization procedure to explore this possibility and show that 40% of the cell-surface CD2 molecules can be specifically co-precipitated in association with the Ti-CD3 complex.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1998

Requirement of CD3 complex-associated signaling functions for expression of rearranged T cell receptor beta VDJ genes in early thymic development.

During alpha beta thymocyte development, the clonotypic alpha beta-T cell receptor (TCR) is preceded by sequentially expressed immature versions of the TCR-CD3 complex: the pre-TCR, containing a clonotypic TCR-beta chain and invariant pre-Talpha, is expressed on pre-T cells before rearrangement of the TCR-alpha locus. Moreover, clonotype-independent CD3 complexes (CIC) appear on pro-T cells before VDJ rearrangements of TCR-beta genes. The pre-TCR is known to mediate TCR-beta selection, the prerequisite for maturation of CD4(-)8(-) double negative (DN) thymocytes to the CD4(+)8(+) double positive stage. A developmental function of CIC has so far not been delineated. In mice single deficient and double deficient for CD3zeta/eta and/or p56(lck), we observe a pronounced reduction in the proportions of CD25(+) DN thymocytes that express intracellular TCR-beta chains. TCR-beta transcripts are reduced in parallel with TCR-beta polypeptide chains whereas no reduction in TCR-beta locus rearrangements could be detected. Wild-type levels of TCR-beta transcripts and of cells expressing TCR-beta polypeptide chains are induced by treatment with anti-CD3epsilon mAb. The data suggest that the initial expression of rearranged TCR-beta VDJ genes in pro-T cell to pre-T cell progression is dependent on CD3 complex signaling, and thus define a putative developmental function for CIC.

Animals↗
PubMed1996

Cloning, sequencing and expression of the bovine CD3 epsilon and TCR-zeta chains, two invariant components of the T-cell receptor complex.

CD3 epsilon and the zeta-chain of the bovine T-cell receptor (TCR) are two invariant molecules with an important role in signal transduction via the TCR/CD3 complex. The nucleotide sequence of a bovine CD3 epsilon cDNA clone containing the complete coding sequence was determined and the deduced amino acid (aa) sequence compared to that of other species. The cytoplasmic domains of the different CD3 epsilon clearly show a higher degree of conservation than the extracellular domains. Bovine CD3 epsilon produced in Escherichia coli using different bacterial expression vectors was recognised by antibodies (Ab) directed against the intracytoplasmic domain of human CD3 epsilon. A partial bovine TCR zeta-chain cDNA was generated by the polymerase chain reaction (PCR) using primers that were based on sequences that are conserved between different species; 3' and 5' RACE-PCR were carried out to obtain the complete TCR zeta-chain cDNA sequence. A comparison of the predicted TCR zeta-chain aa sequence reveals that the GDP/GTP-binding motif, which is conserved in other species, shows marked differences in the bovine and ovine TCR zeta-chains. In contrast to CD3 epsilon, the short extracellular domain of the TCR zeta-chain is 100% conserved between the different species and the transmembrane domain also shows a high degree of identity. Ab were raised against the TCR zeta-chain, produced as a glutathione S-transferase fusion protein in E. coli, and were used in Western blot analysis to further characterise TCR zeta-chain expression in T-cells. The regents provide valuable tools for the study of signal transduction pathways in normal and transformed bovine T-cells.

Amino Acid Sequence↗
PubMed1998

A novel 90-kDa tyrosine-phosphorylated protein associated with TCR complex in thymocytes.

Ligation of the TCR-CD3 complex initiates a cascade of tyrosine phosphorylation that results in T cell activation. Initial activation of tyrosine kinases depends on the phosphorylation of activation motifs on CD3 chains. We previously found that a 90-kDa protein was tyrosine phosphorylated upon TCR cross-linking and the induction of the phosphorylation was dependent on the structure of the CD3 complex. In this study, we further characterized p90 phosphorylation. Phosphorylation of p90 was induced only by stimulation through the TCR-CD3 complex but not by other kinds of stimulation including CD28- or hydrogen peroxide-mediated activation and was dynamically regulated. Phosphorylated p90 was associated with the TCR-CD3 complex upon T cell activation. In a normal T cell population, thymocytes but not splenic T cells induced the tyrosine phosphorylation of p90 upon TCR cross-linking. These results suggest that p90 is a novel phosphoprotein associated with the TCR-CD3 complex and may play a role in TCR signaling during thymocyte differentiation.

Animals↗
PubMed1994

Transition from TCR-beta dimer to TCR-alpha beta-expressing cells by introduction of an alpha-chain in an immature thymocyte cell line.

The molecular basis for the surface expression of TCR-beta chain in the absence of association with TCR-alpha, -gamma, or -delta chain by an immature thymocyte cell line was investigated. The TCR-beta chain expressed by this cell line was not encoded by any unique DNA sequence, nor was it inserted into the membrane via a glycosyl-phosphatidylinositol linkage. Transfection of two other beta-chains derived from mature T cell clones resulted in the surface expression of dimers of the transfected beta-chains in both cases. Immunoprecipitation of the beta-dimer-CD3 complex demonstrated that the association of the beta-dimer with the CD3 complex, especially the CD3 zeta chain, was so weak that they dissociated under the detergent conditions in which the TCR-CD3 complex of mature T cells is kept intact. Transfection of TCR-alpha chain resulted in the expression of a TCR-alpha beta-CD3 complex and the disappearance of beta-dimers. In accordance with the changes in TCR complex components, the association between TCR-alpha beta and CD3 complex became stable and the cells transduced signals more efficiently. The results demonstrate that the expression of TCR-beta as part of an incomplete TCR-CD3 complex is developmentally regulated and the expression of TCR-alpha chain results in normal configuration and function of TCR complex.

Animals↗
PubMed2003

[Study on corelation between InsP(3) generation and TCR/ CD3 complex-mediated [Ca(2+)]i responses in T cells from SLE patients].

AIM: To demonstrate whether function disorder of T cells from SLE patients was relative to abnormal biochemical pathways mediated by TCR/ CD3 complex and whether this abnormality was relative to the InsP(3) production. METHODS: Human T cells were isolated through Nylon-columns from heparinized peripheral blood from SLE patients and control individuals. Percentage of CD3(+) T cells was detected by flow cytometry. After cross-linking of anti-CD3 mAbs to sheep anti-mouse IgG and stimulating T cells, the changes of free calcium ion within T cells was observed successively for 10 minutes by an adhesion cytometry. Flow cytometry was used to detect the difference in positive rate between normal individual's and SLE patient's T cells. Level of InsP(3) was detected by a radioreceptor assay kit. RESULTS: (1)Flow cytometry analysis showed that CD3(+) T cells obtained through nylon column accounted for more than 90%.(2)The base line recordings of [Ca(2+)]i response from SLE patients were similar to that from normal control (P=0.105). Peak and plateau [Ca(2+)]i response in T cells of SLE patients were significantly higher than that in the control group (P<0.001). (3)The percentage of the CD3(+) T cells was similar in both individuals (P=0.665).(4)No differences in the anti-CD3 mAb-mediated InsP(3) generation were found between the two groups (P=0.537). CONCLUSION: TCR/ CD3-mediated [Ca(2+)]i responses in T cells from SLE patients is abnormal, and the abnormality has no relation to InsP(3) generation.

Animals↗
PubMed1989

T-cell receptor-CD4 physical association in a murine T-cell hybridoma: induction by antigen receptor ligation.

By employing flow cytometric analysis and fluorescence resonance energy transfer (FRET), we examined the physical relationship between the T-cell receptor-CD3 complex (Ti-CD3) and the CD4 molecule on helper T cells. Through the use of an L3T4-negative murine T-cell hybridoma infectant expressing the human CD4 gene and having antigen specificity for HLA-DR, we show that binding of the Ti-CD3 complex with an anti-CD3 monoclonal antibody induces its redistribution proximal to cell-surface CD4. FRET efficiency was 9.4% on cells labeled with rhodaminated anti-CD3 and fluoresceinated anti-CD4. FRET was found to be temperature dependent, since similarly treated cells held at 4 degrees C displayed a FRET efficiency of less than 1%. Energy transfer was evident within 3 min after warming cells to 37 degrees C. Energy transfer was not detected between Ti-CD3 and the abundantly expressed leukocyte common antigen (CD45). Of greater significance was our observation that hybridomas infected with a truncated CD4 gene lacking the cytoplasmic domain failed to transfer energy despite the fact that CD4 was expressed on the cell surface at levels equivalent to or greater than the wild type. These studies suggest that after crosslinking of the Ti-CD3 on CD4+ T cells, a physical association occurs between the antigen receptor complex and CD4 and that the association is dependent upon the presence of the cytoplasmic domain of CD4.

Animals↗
PubMed1996

Tyrosine phosphorylation and recruitment of ZAP-70 to the CD3-TCR complex are defective after CD2 stimulation.

CD2 has been described as an alternative transduction pathway sharing the same biochemical cascade as CD3. The T cell-specific protein tyrosine kinase (PTK) ZAP-70 is believed to play a key role in early tyrosine phosphorylations of cellular proteins induced by CD3 stimulation. We show in the present report that ZAP-70 is insignificantly tyrosine phosphorylated and recruited to CD3 after CD2 stimulation in Jurkat T cells. The same result is obtained for p72syk, a PTK structurally and functionally related to ZAP-70. Several studies have suggested a model in which p56lck would be responsible after CD3 triggering for the phosphorylation of particular tyrosine residues in the immunoreceptor tyrosine-based activation motifs of the CD3 chains, inducing the recruitment and the tyrosine phosphorylation of ZAP-70. In Jurkat cells, p56lck is required for CD3- or CD2-induced tyrosine phosphorylations and clearly activated after CD2 cross-linking. However, we find that the CD3 complex, and especially its zeta-chain, are faintly tyrosine phosphorylated after CD2 triggering. By contrast, CD2 induces PLCgamma-1 tyrosine phosphorylation as efficiently as CD3, with a correlated inositol phosphate production and intracellular calcium increase, and even a higher production of IL-2. Interestingly, the SH2 domains of PLCgamma-1 associate with ZAP-70 upon CD3 stimulation while they bind, in CD2-activated cells, to a heavily tyrosine-phosphorylated 62-kDa protein. Altogether, these findings suggest that CD2 could bypass the PTK ZAP-70 for PLCgamma-1 activation and involves a preferential cascade comprising p56lck and a p62 protein, possibly acting as an anchor molecule.

CD2 Antigens↗
PubMed1998

The regulation of phenotype and function of human liver CD3+/CD56+ lymphocytes, and cells that also co-express CD8 by IL-2, IL-12 and anti-CD3 monoclonal antibody.

The regulation of phenotype and function of human liver infiltrating lymphocytes (LIL) by in vitro culture with IL-2, IL-12 and anti-CD3 monoclonal antibodies (mAb) was investigated. The CD3+ LIL which express 50% less CD3 molecules per cell than peripheral blood T lymphocytes, exhibited a 6-fold reduction in proliferation when stimulated through the CD3 complex by anti-CD3 mAb. LIL freshly isolated or cultured in medium did not suppress MLR response, nor were they cytotoxic. However, treatment of the LIL cells with IL-2, IL-12 and anti-CD3 induced these cells to suppress autologous responding cells in MLR (ca. 70%) and to kill autologous or allogeneic cells. Low level cytotoxicity could be induced by cytokines IL-2, IL-12 or anti-CD3 alone. However, the development of optimum MLR suppression and cytotoxicity induction was dependent upon stimulation of the LIL cells through the CD3 complex. The co-expression of CD3 and CD56 on LIL was also up-regulated by anti-CD3 stimulation in the combination of IL-2 and IL-12. Most of the CD3+/CD56+ cells, also expressed CD8. After the magnetic bead separation procedure, the cytotoxic activity was found mainly in the CD3+/CD56+/CD8+ population. These results suggest that CD3+/CD56+/CD8+ cells can be expanded by stimulation through the TCR/CD3 complex in the presence of IL-2 and IL-12, which results in the suppression of autologous responding cells by a cytotoxic mechanism. The proliferative response of the CD3+/CD56+/CD8+ population was enhanced by the induction of CD1 molecules on the stimulating cells, and anti-CD1 mAb were able to block the response in a dose-dependent manner. The CD3+/CD56+/CD8+ cells were examined for cytokine production by flow cytometry. Cytokines IL-4, TNF-alpha, and IFN-gamma were produced by 91.7%, 29.2%, and 27.4% of the cells, respectively.

Antibodies, Monoclonal↗
PubMed1999

The CD3 epsilon subunit of the TCR contains endocytosis signals.

Ligand binding to TCR induces its internalization and cell surface down-modulation. These phenomena contribute to the extinction of activation signals. Due to the multicomponent nature of the TCR-CD3 complex, its internalization may be mediated by one or several of its subunits. Although it has been reported that CD3 gamma and CD3 delta contain endocytosis motifs involved in the internalization of the TCR-CD3 complex, other subunits could also be involved in this process. For instance, CD3 epsilon and CD zeta display amino acid sequences reminiscent of internalization motifs. To investigate whether CD3 epsilon bears endocytosis signals, we have analyzed the internalization capacity of a panel of deletion and point mutants of CD3 epsilon that were expressed on the cell surface independently of other TCR-CD3 subunits. Here we report that CD3 epsilon displays endocytosis determinants. These data indicate that CD3 epsilon could contribute to the internalization and cell surface down-regulation of TCR-CD3 complexes. Moreover, the existence of endocytosis signals in this polypeptide could serve to retrieve unassembled CD3 epsilon subunits or partial CD3 complexes from the plasma membrane, thus restricting the expression on the cell surface to fully functional TCR-CD3 complexes.

Amino Acid Sequence↗
PubMed1997

Degradation of T cell receptor (TCR)-CD3-zeta complexes after antigenic stimulation.

T cell activation by specific antigen results in a rapid and long-lasting downregulation of triggered T cell receptors (TCRs). In this work, we investigated the fate of downregulated TCR- CD3-zeta complexes. T cells stimulated by peptide-pulsed antigen-presenting cells (APCs) undergo an antigen dose-dependent decrease of the total cellular content of TCR-beta, CD3-epsilon, and zeta chains, as detected by FACS(R) analysis on fixed and permeabilized T-APC conjugates and by Western blot analysis on cell lysates. The time course of CD3-zeta chain consumption overlaps with that of TCR downregulation, indicating that internalized TCR-CD3 complexes are promptly degraded. Inhibitors of lysosomal function (bafilomycin A1, folimycin) markedly reduced zeta chain degradation, leading to the accumulation of zeta chain in large Lamp1(+) vesicles. These results indicate that in T cell-APC conjugates, triggered TCRs are rapidly removed from the cell surface and are degraded in the lysosomal compartment.

Amino Acid Sequence↗
PubMed1992

Interaction of pertussis toxin with human T lymphocytes.

The binding of pertussis toxin (PT) to the human T-cell line Jurkat was examined by using flow cytometry. Fluorescein isothiocyanate (FITC)-labeled PT bound rapidly to the cells in a specific manner as determined by blocking experiments with unlabeled toxin, B oligomer, and the S2-S4 and S3-S4 dimers. Monoclonal antibodies against the S3 subunit of the toxin also significantly inhibited the binding of FITC-PT. Sialidase treatment of the cells resulted in decreased binding of FITC-PT, indicating that sialic acid residues are involved in the binding process. In addition, we studied the effect of PT binding on the expression of cell surface molecules. On binding of PT to the cell surface, a rapid down-regulation of the T-cell receptor (TCR)-CD3 complex was observed. The modulation of the TCR-CD3 complex was independent of the toxin's enzymatic activity, as the B oligomer and a nonenzymatic toxin mutant induced modulation comparable to that caused by the native holotoxin. Isolated dimers did not cause down-regulation. Stimulation of the TCR-CD3 complex, leading to reduced cell surface expression of this complex, provides a possible explanation for the second messenger production associated with the interaction of PT or B oligomer with T lymphocytes. We therefore conclude that PT activates T cells by divalent binding to the TCR-CD3 complex itself or by binding a structure closely associated with it.

Antibodies, Monoclonal↗
PubMed1993

Regulation of thymocyte development through CD3. II. Expression of T cell receptor beta CD3 epsilon and maturation to the CD4+8+ stage are highly correlated in individual thymocytes.

Recent studies have shown that maturation of CD4-8- double negative (DN) thymocytes to the CD4+8+ double positive (DP) stage is dependent on expression of the T cell receptor (TCR)-beta polypeptide. The exact mechanism by which the TCR-beta chain regulates this maturation step remains unknown. Previous experiments had suggested that in the presence of some TCR+ thymocytes, additional DN thymocytes not expressing a TCR-beta chain may be recruited to mature to the DP stage. The recent demonstration of an immature TCR-beta-CD3 complex on early thymocytes lead to the alternative hypothesis that signal transduction through an immature TCR-CD3 complex may induce maturation to the DP stage. In the latter case, maturation to the DP stage would depend on the expression of TCR-beta-CD3 in the same cell. We examined these two hypotheses by studying the expression of the intra- and extracellular CD3 epsilon, CD3 zeta, and TCR-beta polypeptides in intrathymic subpopulations during embryogenesis. CD3 epsilon and CD3 zeta were expressed intracellularly 2 and 1 d, respectively, before intracellular expression of the TCR-beta chain, potentially allowing immediate surface expression of an immature TCR-beta-CD3 complex as soon as functional rearrangement of a TCR-beta gene locus has been accomplished. Calcium mobilization could be induced by stimulation with anti-CD3 epsilon mAb as soon as intracellular TCR-beta was detectable, suggesting that a functional TCR-beta-CD3 complex is indeed expressed on the surface of early thymocytes. From day 17 on, most cells were in the DP stage, and over 95% of the DP cells expressed on the TCR-beta chain intracellularly. At day 19 of gestation, extremely low concentrations of TCR-beta chain and CD3 epsilon were detectable on the cell surface of nearly all thymocytes previously thought to be TCR-CD3 negative. These findings strongly support the hypothesis that maturation to the DP stage depends on surface expression of and subsequent signal transduction through an immature TCR-beta-CD3 complex and suggest that maturation to the DP stage by recruitment, if it occurs at all, is of minor relevance.

Animals↗
PubMed1998

Molecular cloning of pTAC12 an alternative splicing product of the CD3gamma chain as a component of the pre-T cell antigen-receptor complex.

We have reported that a 12-kDa molecule (pTAC12 as a pre-T cell receptor (TCR)-associated chain) was associated as a dimer with the pre-TCR complex as well as the clonotype-independent CD3 complex on the cell surface of immature thymocytes. We now report by protein sequencing and molecular cloning that pTAC12 is an alternatively spliced product of the CD3gamma chain lacking exon 4 containing the transmembrane region. The transcript of pTAC12 is expressed in most T cell lineages and parallels the expression of CD3gamma. However, the pTAC12 protein is expressed on the cell surface of immature thymocytes but not mature T cells, despite the fact that mature T cells express a low level of pTAC12 in association with the TCR complex within the cells. These results indicate that pTAC12 may play a special role for the transport/expression and assembly of the pre-TCR.CD3 complex as well as the clonotype-independent CD3 complex in immature thymocytes.

Alternative Splicing↗
PubMed1996

Physical and functional association of CD45 and CD3-TCR complex on CD1+ human thymocytes. Evidence that the engagement of CD45 molecules can prevent CD1+ thymocytes from apoptosis.

In this study the effects of CD45 engagement on CD3-TCR-driven stimulation of CD1+ human immature thymocytes have been analyzed. Simultaneous cross-linking of CD45 and CD3 antigens on highly purified CD1+ thymocytes reduced the number of cells undergoing apoptosis after 16 h of in vitro culture. This cell population might represent immature thymocytes committed in vivo to die by programmed cell death (PCD). CD45 engagement could also increase the number of cycling CD1+ thymocytes; of note, the large majority (> 95%) of dividing cells expressed the CD1 molecule at the cell surface, indicating that proliferating cells were actually represented by immature thymocytes. These data suggest that the CD45 molecule might play a role in the rescue of immature thymocytes from PCD during differentiation. Along this line, we found that activation of CD1+ thymocytes via the CD3-TCR complex could be enhanced by CD45, both in terms of transcription and surface expression of IL-2R. These effects might be explained by the finding that the CD45 molecule (but not its isoforms CD45RO and RA) was physically associated with the CD3-TCR complex at the cell surface of CD1+ human thymocytes, as shown by co-precipitation and co-capping experiments. Finally, cross-linking of CD45 and CD3 antigens led to the expansion of CD3+ thymocytes co-expressing CD4 and CD8, indicating that simultaneous engagement of CD45 and CD3 molecules can block CD1+ cells at the double-positive (CD3+CD4+CD8+) differentiation stage. On the other hand, stimulation through CD3 resulted in the expansion of thymocytes showing a mature phenotype (CD3+CD4+ or CD3+CD8+). Altogether, these findings suggest that the CD45 molecule is involved both in early activation and in the regulation of CD1+ thymocyte differentiation.

Antibodies, Monoclonal↗
PubMed1993

Characterization of the progression signal for human T-cell proliferation provided by monoclonal antibodies to the CD3-TCR complex.

Following T-cell activation, two distinct stages in the proliferative response can be identified. The first stage or state of competence (G0 to G1 transition) is defined by the acquisition of the ability of activated T cells to proliferate in response to growth factors. The second or progression phase relates to the progression of cells to DNA synthesis in response to exogenous growth factors (e.g., IL-2) or inducers of growth factor synthesis (e.g., phorbol esters). In the present manuscript we provide evidence that soluble monoclonal antibodies (mAbs) to CD3 or the T-cell receptor (TCR), similar to the phorbol esters, can induce IL-2 production and cell proliferation in competent but not resting T cells. The data indicate the role of CD3-TCR complex triggering not only as an "activating or competence signal" but demonstrate its capacity to signal in the progression phase as well. However, there were distinct differences when competent T cells were stimulated by phorbol ester compared to soluble antibodies to CD3 or TCR. Antibodies to the CD3-TCR complex, when compared to phorbol ester, induced less proliferation in competent, memory T cells (CD45RO) than in competent, naive T cells (CD45RA). In contrast to phorbol ester, the induction of IL-2 transcription and cell proliferation in competent cells by soluble mAbs BMA 031 (anti-alpha/beta T-cell receptor) or OKT3 (anti-CD3) was inhibited by cyclosporin A (CsA). This implies that in activated T cells there is a step between activation of the CD3-TCR complex and the point(s) of action of phorbol ester that is susceptible to CsA in activated cells. Alternatively, the data may indicate involvement of different regulatory elements with different sensitivities to CsA for the induction of IL-2 transcription by phorbol ester or antibodies to the CD3-TCR complex.

Antibodies, Monoclonal↗
PubMed2000

Molecular mechanism of the impairment in activation signal transduction in CD4(+) T cells from old mice.

It is well known that IL-2 production of CD4(+) T cells from old mice (old T cells) is impaired. In this study, we have examined TCR complex zeta chain expression of old T cells and their TCR downstream signal transduction pathways stimulated with anti-CD3. Activation of protein tyrosine kinases, Fyn and ZAP-70, and turnover of inositol phosphates stimulated with anti-CD3 were severely impaired in old T cells, although levels of these proteins were comparable to those in young T cells. Increase in intracellular Ca2+ concentration in old T cells was also impaired. Old T cells starting the Ca(2+) oscillation by the anti-CD3 stimulation were severely decreased in number and the oscillation waves were broader in shape. T cells with zeta-FcvarepsilonRgamma heterodimer in the TCR-CD3 complex were increased in proportion in old T cells with a concomitant decrease in the T cells with zeta-zeta homodimer. The density of the TCR-CD3 complex on old T cells was confirmed to be comparable to that on young T cells. The impairment in TCR downstream signal transduction pathways and the increase in zeta-FcvarepsilonRgamma heterodimer in the TCR-CD3 complex were confirmed to be the situation in Th1 clones established from old mice. These results indicate that old T cells are impaired in response to TCR stimulation, because T cells with the TCR-CD3 complex containing the zeta-FcvarepsilonRgamma heterodimer are increased in proportion in old T cells.

Aging↗