Search

Interleukin-2 (IL-2) belongs to a series of mediators that are produced by T cells and exert multiple, pleiotropic effects in an autocrine or paracrine fashion. IL-2 plays a fundamental role in the ontogeny of developing T cells in the thymus and supports the growth or effector function of a wide array of immunologically relevant cells, including macrophages and B and NK lymphocytes, as well as a variety of different T-cell subpopulations. Nonetheless, the function of this lymphokine must be highly controlled in vivo to avoid systemic effects that might endanger the specificity of an immune response and result in autoimmune reactions. Accordingly, various mechanisms guarantee compartmentalization of IL-2, that is, chronological and spatial restriction of IL-2 production, bioavailability, and state of responsiveness. The secretion of IL-2, as well as the expression of the two components of the high-affinity IL-2 receptor (IL-2R), are developmentally controlled during ontogeny and, within the cellular immune system, are restricted to defined pre- and intrathymic stages of immature T cells or T-cell precursors. In the peripheral lymphoid organs, IL-2 is produced by a defined population of mature CD4+ T lymphocytes in which the IL-2 gene is transcribed or silenced, depending on the combination of antigenic and nonspecific activation signals to which the cell is exposed. Thus, the absence of certain costimulatory signals leads to a long-lasting inactivation of the IL-2 gene, a phenomenon that accompanies nondeletional T-cell tolerance. IL-2 has a short half-life and is secreted in apposition to the cell with which the T cell interacts. Expression of the high-affinity IL-2R is activation-dependent in most cell types. Thus, different mechanisms, intervening in all compartments relevant for the action of IL-2, together contribute to a restriction of IL-2 effects, conferring a relative specificity to this pleiotropic mediator.

The association of alkaline phosphatase (ALPase) with the cytoskeleton in lymphoid cells was investigated. Extracting cells with non-ionic detergents such as Triton, we determined that ALPase is present in the cytoskeletal fraction in fully differentiated B lymphocytes, X63 myeloma cells and Sp2/O hybridoma cells. During the course of B-lymphocyte activation, the ALPase shifted from a soluble to a Triton-insoluble form. Changes in the phosphorylation of Triton-insoluble proteins with molecular weights of 120, 100, 90, 75, 34 and 31 kDa were detected, coinciding with the appearance of the ALPase in this fraction. The possible role of ALPase in the differentiation of B cells is discussed.

Developing T cells diverge to several different effector classes, identified by their ability to express different set of genes. Aside from the genes encoding components of the TCR/CD3, there are many others that are activated and/or inactivated during T-cell development, but the functions of most of them are not yet defined. Despite the significant progress made, several fundamental aspects of the major steps of T-cell differentiation remains unclear. Thus, while long ago it was realized that the thymus is a central organ for the development of functionally competent T lymphocytes, it appears clear today that ectopic T-cell differentiation can also take place. In this article we review some of the molecules implicated in T-cell development and discuss some of the pathways that lead to mature T cells from precursors, both intra- and extra-thymically, as well as their implications in the acquisition of self tolerance.

Idiotypic cross-reactivities between T and B cell receptors have been taken in the past to suggest VH-gene expression by both types of lymphocytes. More recently, after the molecular characterization of TcR, those observations were reinterpreted to indicate idiotypic network regulation, operating to select cross-reactive idiotypes in both B and T cell compartments. In support of these views, it has been shown that T cell expression of idiotypes is controlled by IgH-linked genes and markedly altered in B cell-deprived mice, and that T cells "learn" idiotype expression from the B cell compartment in the first few weeks of life. In most of these studies, aleatory idiotype cross-reactivities have not been sufficiently considered. Given the large diversity of antibodies and TcR, and the degeneracy of antibody-ligand interactions, it could be expected that a (monoclonal) anti-idiotypic reagent prepared against an antibody idiotope will always "cross-react" with some TcR variable regions. If these will be "major" T cell clonotypes, situations of idiotype sharing by B and T cells can be found which indicate neither VH-gene expression by T cells nor idiotypic network regulation. We report here one example of such aleatory expression of antibody idiotypes by T lymphocytes. A monoclonal anti-idiotypic antibody directed to anti-TNP antibodies of BALB/c mice specifically inhibits the growth and effector activity of C57BL/6 anti-NP-self helper T cells, while failing to interact with either BALB/c anti-NP-self or C57BL/6 anti-TNP-self helper cells. The clonotypic nature of these interactions could also be demonstrated by the specific induction of IL-2 production in the appropriate helper T cells by the anti-idiotypic antibody.(ABSTRACT TRUNCATED AT 250 WORDS)

Helper T cells directed to B cell surface determinants activate their "targets" into polyclonal antibody production in vitro and in vivo, but B cells which bind to epitopes on the helper cell surface are preferentially induced. Furthermore, "anti-helper" B cell activation also occurs by "back-stimulation", that is even when the responding B lymphocytes are not specific targets for the inducing helper cells, as long as these are simultaneously activated by appropriate interactions with presenting cells. In our experimental systems, this is the only condition where "bystander" activation can be recorded. These findings suggest mechanisms of auto-antibody production associated with unrelated helper cell activity in vivo.

Hematopoietic precursors lacking T cell antigen receptors (TCR-CD3-) and CD4 and CD8 surface markers (i.e. double-negative thymocytes) give rise to functionally mature T lymphocytes. Yet their major progeny are immunologically unresponsive thymocytes in spite of having acquired TCR-CD3 and CD4-CD8. Because only mature thymocytes migrate to peripheral lymphoid organs and most thymocytes die in situ, the knowledge of the events associated with functional maturation in the double-negative thymocyte progeny is a fundamental question in T cell development. We reasoned that a clue to trace the fate of early human thymocytes may perhaps come from the study of the developmental acquisition of CD1 antigen, currently used to define better the functionally inert CD4+8+ (double-positive) stage and absent in mature, medullary thymocytes and peripheral T cells. By using antibodies specific for CD1 (HTA 1/T6) we show here that a large fraction of double-negative thymocytes also express CD1. CD1+3-, CD1+3+, CD1-3+, and CD1-3- subsets all exist. The CD1+3- subset generates CD1+3-4-8+ precursors of CD1+ double-positive cells. A large portion of the CD1+3+ subset bears TCR gamma delta-CD3 complexes. The CD1- subsets are responsive in assays of function, in which they can be stimulated to use the interleukin 2 pathway of proliferation and to mediate cytotoxicity. In contrast, all CD1+ thymocytes behave as functionally inert cells. Thus, the CD1 surface marker delineates human thymocyte precursors and their products which lack, or possess, functional potential in vitro, on both alpha beta and gamma delta lineages.

Mitogenic membrane ligands have been shown to activate interleukin 2 (IL2) production only in mature T cells, IL2 constitutive secretion having not yet been demonstrated. Here we have isolated a population of T11+3-4-6-8- human thymocytes and CD7+/T11-3-4-6-8- prothymocytes which produce and consume IL2 upon phytohemagglutinin triggering. Interestingly, their proliferation in the absence of any exogenous stimulating agent was related to an autonomous use of the IL2 system (IL2 secretion and binding to its specific receptor, whose constitutive, functional expression in human early thymocytes was recently shown). The internal activation of this system before T cell receptor acquisition stresses the relevance of the understanding of the alternative activation pathway(s) in T cell development. These findings, together with the demonstration of IL2-promoted differentiation of human early thymocytes into mature T cells, suggest that IL2 may also be a growth and differentiation factor acting specifically early in T cell development.

A T3 complex-bearing subpopulation was characterized within an in vivo cycling T4-8- early thymocyte compartment which contains cells constitutively expressing interleukin 2 and transferrin receptors. We show differentiation in vitro of both mature subsets of thymocytes (T3+4+8- and T3+4-8+) from the above T4-8- compartment, their appearance being preceded by cells in a T3+4-8- intermediate stage. Furthermore, those mature thymocytes generated in vitro contain functionally competent cells which use T3, T4 and T8 structures for their cytolytic activity. The finding of T3+4-8- thymocytes in vivo, together with the observation that T3 antigen expression precedes that of T4 or T8 molecules in vitro, shows that T3 (and presumably Ti) is present early in ontogeny, and suggests that T3+4-8- cells constitute an "intermediate" stage relevant to the connection between early precursors and mature thymocytes during T lymphocyte ontogeny.

T cell activation induced via the CD3-T cell receptor (TcR) complex, or by triggering of polyclonal antigen-independent pathways, involves both interleukin 2 (IL 2) production and IL 2 receptor (IL 2R) expression and results in T cell proliferation. To assess the potential role of the IL 2 pathway in T cell development, growth and activation requirements of intrathymic T cell precursors were analyzed and correlated with the expression of IL 2R. In contrast to CD3-TcR+ (either CD4+ or CD8+) mature thymic cells, CD3-TcR- CD1-4-8- early prothymocytes constitutively expressed IL 2R and displayed IL 2-mediated proliferation, which was inhibited by anti-IL 2R monoclonal antibodies (mAb). Moreover, prothymocytes developed spontaneous proliferation in the absence of exogenous IL 2, which was also abrogated by blocking of IL 2R with specific mAb. The possibility that both IL 2 production and IL 2R expression are autonomously activated early in T cell development, before acquisition of the CD3-TcR complex, led us to study the implication of alternative pathways of activation at this ontogenic stage. Triggering of the CD2 pathway with mAb against two different epitopes of the molecule (D66 and 9.6/T11(1) induced proliferation of CD3-TcR- prothymocytes in the absence of exogenous IL 2, while proliferation of CD3-TcR+ mature thymocytes required Il 2 supplementation. These data suggest that polyclonal activation of the Il 2 pathway may be selectively operative at early stages of T cell development, being involved in the growth and differentiation of intrathymic T cell precursors.

Activated T lymphocytes proliferate in response to interleukin-2 (IL-2), which binds to a specific high-affinity receptor (IL-2R). This consists of at least two noncovalently linked polypeptides, p55/IL-2R alpha (Tac) and p75/IL-2R beta. Both molecules bind IL-2 independently, with low and intermediate affinity respectively, but only IL-2R beta is thought to mediate IL-2 signal transduction. Although IL-2R beta seems to be constitutively expressed on resting T lymphocytes, the growth of these T cells is specifically induced by antigenic triggering by the T-cell receptor (TCR), which then results in the transcription of both IL-2 and IL-2R alpha genes. By contrast, activation of the IL-2/IL-2R pathway in the thymus seems to precede the appearance of the TCR, as IL-2R alpha is expressed on T-cell precursors lacking TCR. The basis for IL-2R expression by immature thymocytes, however, remains largely unknown. We show here that IL-2R alpha-negative T-cell precursors constitutively express IL-2R beta and produce their own IL-2. The IL-2/IL-2R beta interaction on these cells induces the expression of IL-2R alpha, leading to high-affinity IL-2R display and cellular proliferation. We suggest that this IL-2-dependent autocrine pathway of growth stimulation plays a key role in the intrathymic development of mature T cells.

The role of interleukin 2 (IL 2) and interferon (IFN)-gamma in the maintenance of natural killer (NK)-like activity mediated by human cytolytic T cell clones was investigated. When cultured in standard supernatant (SN) obtained by phytohemagglutinin stimulation of human mononuclear cells (containing both IL2 and IFN activities), several mixed lymphocyte culture-derived clones displayed cytolytic activity directed against the K562 cell line; in addition, some of these clones also lysed specific target cells bearing the sensitizing alloantigens. When cultured in IL2-containing SN obtained from the Jurkat cell line, the NK-like activity was selectively abrogated within 4-5 days. However, by culturing cells again in standard SN the cytolytic activity was completely restored. The possibility that inhibitory molecules in Jurkat SN could be responsible for the loss of NK-like activity was ruled out by experiments showing that cytotoxicity could be induced by mixtures of Jurkat and standard SN. In addition, a source of affinity chromatography-purified IL2 also failed to maintain NK-like activity. Moreover, addition of recombinant IFN-gamma in combination with purified IL2 did not prevent the loss of NK-like activity. The present results indicate that neither IL2 nor IFN-gamma are sufficient to maintain NK-like activity and suggest that other molecule(s) are required.

Supernatants containing interleukin 2 (IL 2) induce strong proliferation and expression of natural killer (NK)-like activity in human thymocytes. Different supernatants were compared for: (a) IL 2 activity, (b) thymocyte proliferation capacity and (c) induction of NK-like cytotoxicity. All these activities were present in a partially purified IL2 preparation obtained by gel filtration chromatography (Mr 15 000-20 000). However, in supernatants from different sources and in the 15 000-20 000-Mr semipurified fractions, we observed that the NK-like cytotoxicity inducer effect did not correlate with either the mitogenicity or the IL2 activity. The presence in the supernatants of interleukin 1 (IL 1), interferon (IFN) or phytohemagglutinin (PHA) does not seem to be a prerequisite for the induction of NK-like cytotoxicity, since this activity was (a) fully present in supernatants devoid of IL 1, IFN and PHA, (b) absent in preparations of IL 1 and (c) not augmented after supplementation of the supernatants with IFN-gamma. We also investigated the cellular characteristics of the precursor thymocytes responsive to IL 2 supernatants. Removal of the T3+ cells at the initiation of the culture abrogated the proliferative response and eliminated the generation of NK-like cytotoxicity. Under the same conditions, removal of the HTA1+ population increased the proliferation and did not affect the NK-like activity. Our results suggest that: (a) either IL 2 is not responsible for the induction of NK-like cytotoxicity or its action is modulated by other molecules, and (b) the precursor-responder population is preferentially included in the mature T3+ subset.

Development of the T cell lineage is characterized by the homing of hematopoietic precursors to thymus, followed by their acquisition of receptors for antigen. T cell receptors are alpha beta or gamma delta heterodimers associated with CD3 (TCR-CD3). Very early T cell precursors in humans have been characterized as CD7+ 45+ cells which lack the T cell differentiation antigens CD1, CD2, CD3, CD4, and CD8. A phenotypically equivalent early thymocyte population also occurs in postnatal life, and we have previously shown that interleukin 2 (IL2) promotes the development in vitro of both the alpha beta and the gamma delta T cells from these early thymocytes. Here we have analyzed the requirements of the induction of the IL2 pathway in early thymocytes, and their developmental potential. We show that: (i) thymic stromal cells, which are present in thymocyte suspensions, are necessary to induce the IL2 pathway and the development of alpha beta or gamma delta T cell lineages from early thymocytes in vitro; and (ii) when removed from the in vivo environment, early thymocytes can develop in vitro into TCR-CD3- cells of the natural killer (NK) lineage. We conclude that CD7+ 45+, CD1-2-3-4-8- early thymocytes are multipotential progenitors that, at least, have the capacity to develop into alpha beta or gamma delta T cell and NK lineages. The analysis of the mechanisms of generation and selection of human T and NK cell diversity, not feasible in bone marrow cultures, is now possible.

As shown previously, idiotype (Id) sharing between anti-2,4,6-trinitrophenyl T helper (Th) cells and antibodies in BALB/c mice results from immunoglobulin (Ig)-dependent selection of the T cell repertoire. In contrast, a clonotype defined by the same F6(51) anti-Id antibody is expressed by C57BL/6 anti-(4-hydroxy-3-nitrophenyl)acetyl Th cells independently of Ig influences. We have now used these systems to test the hypothesis that Ig-dependent Th cell repertoire selection occurs in the compartment of "naturally" activated lymphocytes. "Naturally" activated or resting splenic L3T4+ cells were separated from normal BALB/c and C57BL/6 mice and tested, either directly or after in vitro priming, in hapten-specific helper assays for expression of the clonotope defined by the F6(51) anti-Id antibody. The results show the selective expression of the antibody-dependent T cell Id in the "naturally" activated helper cell compartment. In contrast, when the T cell Id is expressed in the absence of Ig-dependent selection, it is only detected in the resting helper cell repertoire. Furthermore, BALB/c "natural" IgM antibodies with anti-Id specificities similar to F6(51) show functionally relevant interactions with syngeneic "naturally" activated Th cells. These are also characterized by high paratopic/Id degeneracy, as compared to helper cells obtained by conventional immunization. These results demonstrate repertoire differences between the set of (resting) lymphocytes participating in immune responses, vs. those "internally" activated in normal individuals. They also suggest the importance of Id network interactions in the compartment of "naturally" activated T and B cells.

Normal BALB/c mice produce 2,4,6-trinitrophenyl (TNP)-I-Ad specific T helper (Th) cells expressing a receptor heterodimer which share with anti-TNP antibodies an idiotope defined by the F6(51) anti-idiotypic antibody. Expression of this Th idiotype is controlled by major histocompatibility complex and immunoglobulin heavy chain-linked genes and results from antibody-dependent selection of T cell repertoires (Martinez-A. et al., Eur. J. Immunol. 1986. 16: 417). We now present evidence for the recursive nature of T----B cell repertoire selection and suggest that perinatal B cells, present in adult peritoneal cavity, operate in the early phases of this process. Thus, the Th idiotype is absent in BALB/c mice which are either suppressed from birth with anti-mu antibodies, or reconstituted with autologous bone marrow after lethal irradiation as adults. Supplementation of bone marrow reconstitution with syngeneic Thy-1-, Ly-1+ peritoneal B cells, however, selects Th cell repertoires that are undistinguishable from normal mice as to expression of the F6(51) clonotype. This effect is lost after depletion of Ly-1+ cells in the reconstituting Thy-1- peritoneal cell population. Interestingly, large in vivo "naturally" activated Ly-1- splenic B cells can also reconstitute Th idiotype expression if they are isolated from normal, but not from athymic, nude donors. However, transfer of normal large splenic T cells to adult nude mice "educates" the splenic "large B cell" compartment in these animals such that they acquire the ability to recursively select, upon transfer to bone marrow reconstituted recipients, the Th clonotype.(ABSTRACT TRUNCATED AT 250 WORDS)

T cells from patients with B cell chronic lymphocytic leukemia (B-CLL) exhibit defective natural killer (NK) activity. In this study, we have analyzed the cytotoxic-inducer effects of gamma interferon (gamma-IFN) and supernatants containing interleukin 2 (IL 2 sup). T cells from patients with B-CLL were incubated with gamma-IFN or IL 2 sup. gamma-IFN did not modulate the very low or undetectable levels of NK activity present in the T cell population. However, the IL 2 sup induced a potent cellular cytotoxicity against NK-sensitive and NK-resistant tumoral target cells. This cytotoxic inducer effect (a) was present in lectin-free IL 2 sup and in a 15,000- to 20,000-dalton molecular weight fraction obtained by gel filtration chromatography of this supernatant; (b) was directed against NK-sensitive and NK-resistant target cells; (c) was not correlated with the basal levels of NK activity; and (d) was not associated with a development or augmentation of the proportion of lymphocytes with classic NK cell phenotype. Taken together, these results demonstrate that unstimulated T cells from B-CLL patients, incubated briefly (18 hours) with IL 2 sup but not gamma-IFN, have strong NK-like cytotoxicity, despite the lack of classic NK activity.

The differentiation of T lymphocytes inside the thymus results in the acquisition of MHC-restricted specific functions mediated by clonally distributed alpha/beta heterodimeric T-cell receptors (TcR). Genes encoding the alpha and beta subunits of the clonotypic receptor (Ti) are rearranged during thymic ontogeny and expressed in association with the monomorphic CD3 complex. The regulation of the expression of functional TcR along T-cell development is thus crucial to establish the ontogenic events involved in the acquisition and selection of T-cell repertoires. Current views support that CD3-alpha/beta heterodimers are acquired late in ontogeny on developing thymocytes already expressing CD4 and/or CD8 surface molecules, whereas CD4- CD8- early precursors, representing the major population in the embryonic thymus, do not yet express the alpha/beta TcR. However, a novel CD3-associated gamma/delta heterodimer has been recently identified on the surface of this "double negative" subset both in thymocytes and in MHC-unrestricted peripheral T cells, suggesting that alpha/beta and gamma/delta heterodimeric receptors are independently expressed on the surface of distinct thymic subpopulations during T-cell development. In contrast to these results, we report here that a major proportion of CD3+1-4-8- adult human thymocytes, included within the early "double negative" subset, express alpha/beta heterodimeric receptors, as assessed by flow cytometric analysis using a frame-work monoclonal antibody (WT.31) against the alpha/beta TcR complex. These and previous data showing that CD3+1-4-8- "double negative" thymocytes constitute a functional intermediate ontogenic stage in the differentiation of CD3+1-4+8-/CD3+1-4-8+ mature T cells from CD3-1-4-8- early prothymocytes further support the relevance of the CD3+1-4-8- transitional subset as immediate intrathymic precursors of alpha/beta TcR-bearing mature T cells. Therefore, developmental regulation of alpha/beta TcR expression was analyzed at the DNA, RNA, and protein levels in those different thymic subpopulations, defined by both functional and phenotypic criteria. Our results demonstrate that multiple Ti beta gene rearrangements and beta RNA messages are already evident at the early prothymocyte stage. Moreover, expression of relative levels of both Ti alpha and Ti beta functional RNA transcripts, similar to those observed in mature thymic cells, were also present in CD3+1-4-8- thymocytes. According with these data, immunoprecipitation analysis using a specific anti-Ti alpha antisera revealed that both alpha and beta molecules are expressed on CD3+ "double negative" and mature thymocytes, but not in prothymocytes

Immunosuppression in AIDS might be due to the immune response rather than to the pathogenicity of the virus. The basis of the immunosuppression could be molecular mimicries involving viral gp-110, CD4 molecules, antibodies, and CD4-acceptor sites. Whether an individual develops auto-immunosuppressive responses or mounts a harmless defence against (or coexists with) the virus follows the general rules of lymphocyte repertoire selection. MHC and V region genes and other polymorphic loci, together with the previous state of the immune system, particularly at early developmental periods, are factors that influence the response. Vaccination against gp 110-HIV might thus protect against infection but at the same time cause auto-immunosuppression and disease.

The monoclonal antibody F6(51), directed to an idiotope of MOPC 460-like anti-1,4,6-trinitrophenl (TNP) antibodies produced in IgHa mouse strains, identifies in helper T cells from C57BL/6 (IgHb) mice with (4-hydroxy-3-nitrophenyl)acetyl (NP)-self specificity, a clonotypic determinant functionally and biochemically associated with the specific T cell receptor. The expression of this antibody-related T cell clonotype in C57BL/6 mice, although "recurrent", is independent of network selection, as shown by its presence in B mice suppressed from birth with anti-mu antibodies, and in IgH-congenic mouse strains. These results indicate aleatory cross-reactivity between T cell receptors and antibodies and command caution in network interpretations for "idiotype sharing".

Alkaline phosphatases (ALPase) (orthophosphoric-monoester phosphohydrolase, EC 3.1.3.1) are implicated in many biologic phenomena including ossification and differentiation of human neutrophils and choriocarcinoma cells. Another trait, demonstrated by microinjection into Xenopus oocytes, is their ability to block the first mitotic division. Previous work in our laboratory has established that ALPase is also present on murine B lymphocytes activated by either polyclonal mitogens or Th cells. We have now characterized the ALPase present on murine B cells as belonging to the liver-bone-kidney isoenzyme and found it to be implicated in B cell differentiation into antibody secretion. Thus, B cell proliferative responses, elicited either by high concentrations of rabbit anti-IgM antibodies or by LPS in the presence of PMA, are characterized by the lack of both antibody secretion and expression of ALPase activity. In contrast, B cells stimulated to differentiate into Ig-secreting cells by B cell differentiation factors, nearly in the absence of a proliferative response, express high levels of ALPase activity, as did those that were LPS-stimulated. These data showing the association of the ALPase expression with the process of B cell differentiation into antibody-secreting cells are discussed in the context of the possible role that phosphorylation-dephosphorylation mechanism may play in controlling the growth/differentiation rate in the B cell lineage.

Up to 75% of 2,4,6-Trinitrophenyl (TNP)-self-specific helper T cells from normal BALB/c mice share a clonotypic determinant with the anti-TNP myeloma protein MOPC 460, recognized by the monoclonal antibody F6(51). Immunization of adult BALB/c mice with the MOPC 460 idiotype (Ab2 mice) leads to high titers of circulating anti-idiotypic antibodies but has no influence on the expression of the T cell clonotype. In contrast, TNP-self-specific helper cells prepared in progenies from Ab2 females, or in BALB/c mice treated as neonatals with anti-idiotypic antibodies, fail to express the corresponding T cell clonotype when immunized as adults. These results demonstrate the idiotype-dependent selection of T cell repertoires early in life and their stability in adults.

Sharing of "idiotypes" by T and B cells with similar nominal specificities has been extensively reported in functional assays. The recent molecular characterization of T cell receptors has led to the suggestion that such idiotypic mimicries could result from "network" selection of available T cell repertoires. Alternatively, the validity of the conclusions taken from those functional assays could be questioned. We have now used an experimental system where recurrent expression of antibody idiotypes by T helper cells requires "learning" from the B cell/antibody compartment, and show here that the idiotypic determinants in question are indeed associated with T cell receptor molecules. A monoclonal antibody (F6(51)) directed to an idiotope of the TNP-binding BALB/c myeloma protein MOPC460 specifically inhibits antigen-dependent proliferation and helper activity of BALB/c anti-TNP-BALB/c helper T cells. The anti-idiotypic antibodies also induce IL-2 production by these helper cells and precipitate a surface molecule with characteristics of T cell receptor. We conclude that, in this particular system, T cell receptors and antibodies of similar nominal specificities share idiotypic determinants.