Antigen-specific human T-cell clones: development of clones requiring HLA-DR-compatible presenting cells for stimulation in presence of antigen.

Sredni, Benjamin; Volkman, David J.; Schwartz, Ronald H.; Fauci, Anthony S.

doi:10.1073/pnas.78.3.1858

Cited by 66 publications

(16 citation statements)

References 32 publications

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“…It is hoped that the recent development of antigen-specific T cell clones (38) may make the answer to this fundamental question in human immunobiology more approachable.…”

Section: Discussionmentioning

confidence: 99%

Antigen-induced human T cell help. Precursor frequency, radiation sensitivity, and allogeneic effects.

Lane¹,

Whalen²,

Fauci³

1983

J. Clin. Invest.

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A B S T R A C T We have recently noted marked differences between the in vitro responses of human B lymphocytes to stimulation with soluble antigens vs. stimulation with mitogens. In the present study, these differences were analyzed in terms of the precursor frequencies for the T cells and B cells involved and in terms of the radiation sensitivity of the T cells providing help in the two systems. Marked differences were found between antigen-induced and mitogen-induced systems with regard to T cell precursor frequencies and radiation sensitivity. In contrast, the precursor frequencies for the B cells involved in the two systems were approximately the same. In addition, having developed a system for the study of human antigen-specific B cell responses, we were interested in delineating the nature of the allogeneic effects that might be operative in this system. Marked allogeneic effects, both positive and negative, were noted in this system and will need to be taken into account in any studies that try to address the question of the genetic restriction, if any, that exists in human antigen-specific T cell-B cell collaboration.Appreciation of the marked differences between the antigen-specific and mitogen-induced activation and immunoregulation of human B cell responses will be of importance in understanding the relationship between specificity and nonspecificity of antibody production in normal and disease states. INTRODUCTIONT cell regulation of B cell reactivity is an area of major interest and importance in both animal and human systems. With the recent availability of several systems Address all correspondence to Dr. H. Clifford Lane. Received for publication 20 January 1983 and in revised form 30 March 1983. to study human B cell function in vitro, considerable interest has centered around the precise nature of the T cell regulation of human B cell responses in both polyclonal and antigen-specific assay systems. Unfortunately, there have been conflicting data among sev-. eral of these systems (1-10). Of particular note has been the divergence of results with regard to the radiosensitivity of T cell help and the relative contributions of allogeneic effects in the mitogen-induced vs. antigen-induced human B cell systems. Disagreement with regard to this latter point has led to difficulty in delineating the precise nature of genetic restrictions in T cell-B cell collaboration in antigen-specific responses as well in appreciating the scope of allogeneic effects in co-culture experiments now commonly used in the study of patients with immunemediated or immunodeficiency diseases.Recently, in vitro systems have been developed for the study of antigen-induced, antigen-specific antibody production and secretion into culture supernatants by human B cells (11)(12)(13)(14). The use of enzymelinked immunosorbent assays (ELISA)l has proven to be extremely useful in these studies because of their simplicity, sensitivity, and specificity. These advances have allowed for a more precise study of the mechanisms involved in...

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“…It is hoped that the recent development of antigen-specific T cell clones (38) may make the answer to this fundamental question in human immunobiology more approachable.…”

Section: Discussionmentioning

confidence: 99%

Antigen-induced human T cell help. Precursor frequency, radiation sensitivity, and allogeneic effects.

Lane¹,

Whalen²,

Fauci³

1983

J. Clin. Invest.

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“…The human T-cell clones CT8111, CT411, and RW17C were obtained from a single donor's peripheral blood mononuclear cells, cloned, and maintained in culture as described (13,14). Briefly, the cytotoxic clones CT8111 and CT411 have a target specificity for class I and class II alloantigens, respectively, both of which are present on the Epstein-Barr virus-transformed human lymphoblastoid B cell line Laz 156 (1, 2, 14, 15).…”

Section: Methodsmentioning

confidence: 99%

Triggering of the T3-Ti antigen-receptor complex results in clonal T-cell proliferation through an interleukin 2-dependent autocrine pathway.

Meuer¹,

Hussey²,

Cantrell³

et al. 1984

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

429

162

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Human T-cell clones and anti-T-cell-receptor antibodies (clonotypic) directed at surface receptors for antigen (T3-Ti molecular complex) as well as anti-interleukin 2 (IL-2) and anti-IL-2-receptor antibodies were utilized to investigate the mechanism by which alloantigens or antigen plus self-major histocompatibility complex (MHC) (i.e., physiologic ligand) trigger specific clonal proliferation. Soluble or Sepharose-bound anti-Ti monoclonal antibodies, like physiologic ligand, enhanced proliferative responses to purified IL-2 by inducing a 6-fold increase in surface IL-2 receptor expression. In contrast, only Sepharose-bound anti-Ti or physiologic ligand triggered endogenous clonal IL-2 production and resulted in subsequent proliferation. The latter was blocked by antibodies directed at either the IL-2 receptor or IL-2 itself. These results suggest that induction of IL-2 receptor expression but not IL-2 release occurs in the absence of T3-Ti receptor crosslinking. Perhaps more importantly, the findings demonstrate that antigen-induced proliferation is mediated through an autocrine pathway involving endogenous IL-2 production, release, and subsequent binding to IL-2 receptors.Recent studies using cloned antigen-specific T lymphocytes and monoclonal antibodies directed at their various surface glycoprotein components have led to identification of the human T-cell-antigen receptor as a surface complex comprised of a clonotypic 90-kilodalton (kDa) Ti heterodimer and the monomorphic 20/25-kDa T3 molecule (1, 2). Upon binding to the surface of a clone, monoclonal antibodies to either T3 or its associated unique Ti heterodimer induced rapid loss of the T3-Ti complex, a process termed modulation, and inhibited all antigen-specific functions of a given clone. However, at the same time, these antibodies produced a markedly enhanced clonal proliferative response to interleukin 2 (IL-2)-containing media (1-3). Moreover, when coupled to the surface of a solid support such as Sepharose, the appropriate surface-linked anti-Ti and anti-T3 antibodies were able to induce IL-2 secretion and clonal proliferation, analogous to physiologic ligand (i.e., antigen) itself (4). These findings suggested that clonal proliferation resulting from triggering of the T3-Ti antigen receptor might be mediated through the growth factor IL-2. The latter is a 15-kDa sialoglycoprotein that interacts with activated T cells through specific membrane receptors distinct from the T3-Ti complex and is known to induce T-cell growth upon surface binding (5-12).The present study was performed to examine the relationship between the T-cell-antigen receptor and IL-2-mediated T-cell growth. MATERIALS AND METHODSHuman T-Cell Clones. The human T-cell clones CT8111, CT411, and RW17C were obtained from a single donor's peripheral blood mononuclear cells, cloned, and maintained in culture as described (13,14). Briefly, the cytotoxic clones CT8111 and CT411 have a target specificity for class I and class II alloantigens, respectively, both of which are present...

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“…This procedure was followed until the total number ofviable T cells reached 10-20 X 106. These cells were then seeded at 1 x 105 cells per ml in fresh media with IL 2 and grown for [5][6][7] days in the absence of irradiated fillers prior to testing and fusion. Before fusion, each T cell line was screened for antigen specificity in two ways: (i) TeT-induced T cell proliferation on y-irradiated autologous monocytes and (ii) TeT-induced helper activity on autologous B cells.…”

Section: Methodsmentioning

confidence: 99%

“…Dissection ofthese events has been greatly improved since the discovery of interleukin 2 (IL 2) (3) which supports the in vitro growth of T cells with maintenance of specificity and function (4). As documented with murine T cell lines, human T cells require repeated stimulation with antigen and autologous monocytes to induce proliferation (5,6). Because availability of human autologous monocytes is limited, development of functional T cell hybridomas with autonomous growth potential was attempted.…”

mentioning

confidence: 99%

Antigen-specific human T-cell hybridomas with helper activity.

DeFreitas¹,

Vella²,

Linnenbach³

et al. 1982

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

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Human T cell hybridomas were produced by fusing the hypoxanthine phosphoribosyltransferase-deficient line of the human T cell lymphoma Jurkat with a continuous line of normal human T cells specific for tetanus toxoid (TeT). The hybridomas were selected for their ability to produce interleukin 2 after exposure to TeT on semiautologous monocytes and for their ability to bind to TeT-pulsed semiautologous monocytes. These antigenspecific T hybridomas demonstrated potent helper activity for semiautologous B cells as determined by the production of high levels of anti-TeT antibody in vitro.

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Antigen-specific human T-cell clones: development of clones requiring HLA-DR-compatible presenting cells for stimulation in presence of antigen.

Cited by 66 publications

References 32 publications

Antigen-induced human T cell help. Precursor frequency, radiation sensitivity, and allogeneic effects.

Antigen-induced human T cell help. Precursor frequency, radiation sensitivity, and allogeneic effects.

Triggering of the T3-Ti antigen-receptor complex results in clonal T-cell proliferation through an interleukin 2-dependent autocrine pathway.

Antigen-specific human T-cell hybridomas with helper activity.

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