Surface markers of cytotoxic T lymphocyte clones

Haas, Werner; Boehmer, Harald von

doi:10.1002/eji.1830140421

Cited by 16 publications

(6 citation statements)

References 13 publications

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“…This situation may apply to many of the Lyt-2' L3T4-class II-restricted T-cell clones documented in the literature (9) in which Lyt-2 appears to have no function. In other cases, inhibition studies with anti-Lyt-2 have not been performed (26). However, there does appear to be evidence of functional L3T4 in an unusual class I-restricted hybridoma (20).…”

Section: Discussionmentioning

confidence: 99%

Involvement of Lyt-2 and L3T4 in activation of hapten-specific Lyt-2+ L3T4+ T-cell clones.

Groth¹,

Gallagher²,

Miller³

1986

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

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The murine T-cell surface molecules Lyt-2 and L3T4 play a role in the activation of antigen-specific T cells. The currently accepted model for the function of these molecules proposes that Lyt-2 and L3T4 increase the overall avidity of the interaction between the T-cell antigen receptor and antigen in association with the major histocompatibility complex (MHC) molecules on the antigen-presenting cell. We have used two unusual Lyt-2+ L3T4' class II MHC-restricted T-cell clones to test whether Lyt-2 can substitute for L3T4 when the T-cell antigen receptor is class 11 MHC-restricted. Monoclonal antibodies against L3T4 profoundly inhibited antigen-induced lymphokine production by both T-cell clones. Anti-Lyt-2 monoclonal antibody had no effect. These results strongly suggest that L3T4 and the class 11-restricted T-cell antigen receptors are physically close during antigen recognition, probably as part ofa multimolecular complex from which Lyt-2 is excluded. The ability of L3T4 but not Lyt-2 to participate in such a complex with class 11-restricted T-cell antigen receptors may explain the striking correlation between class II restriction and L3T4 expression in the peripheral T-cell pool.Activation of T lymphocytes depends not only on clonally distributed T-cell antigen receptors (TcR) but also on a number of relatively invariant surface glycoproteins such as Lyt-2 and L3T4 (homologous to the human T8 and T4 antigens, respectively). In general, these two molecules are expressed in a mutually exclusive fashion on mature T cells and have therefore been used to define T-cell subsets.The vast majority of Lyt-2' cells recognize antigen in association with a product of the class I major histocompatibility complex (MHC) genes, whereas expression of L3T4 is characteristic ofthe class II-restricted subset ofT cells (1). At the population level, most of the cytotoxic/suppressor function resides within the Lyt-2' subset, whereas helper capability is a function of the L3T4' subset. However, the correlation between T-cell function and the expression of Lyt-2 or L3T4 is weaker than that between MHC-restriction pattern and Lyt-2/L3T4 expression.Evidence implicating Lyt-2 and L3T4 in T-cell activation comes from antibody-mediated blocking experiments. Antibodies to Lyt-2 can simultaneously inhibit cytotoxicity, proliferation, and lymphokine production by Lyt-2' T-cell clones (reviewed in refs. 2 and 3), suggesting that Lyt-2 is involved in the initial antigen-recognition event. However, there is marked variation in the degree to which anti-Lyt-2 antibodies inhibit activation of individual T-cell clones. Such variation is not a function of the amount of Lyt-2 on the T-cell surface but appears to correlate negatively with the affinity of the TcR for antigen in association with MHC molecules (antigen-MHC). Thus, secondary anti-allo-MHC responses are far more difficult to inhibit than are primary responses (2).Further support for this interpretation has been provided by the observation that anti-viral clones (from a secondary res...

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Section: Discussionmentioning

confidence: 99%

Involvement of Lyt-2 and L3T4 in activation of hapten-specific Lyt-2+ L3T4+ T-cell clones.

Groth¹,

Gallagher²,

Miller³

1986

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

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“…Positive selection ensures that T cells respond to foreign antigens in conjunction with self-MHC molecules [1][2][3]. This is achieved by allowing T cells recognizing self peptides presented by self-MHC molecules to mature, resulting in differentiation of CD4 + CD8 + TCR low double-positive (DP) thymocytes into CD4 + CD8 -TCR high or CD4 -CD8 + TCR high singlepositive (SP) T cells [4][5][6]. Negative selection screens for thymocytes recognizing self peptides with high affinity and leads to elimination or inactivation [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Maturational stage-dependent thymocyte responses to TCR engagement

Kattman¹,

Lukin²,

Oh³

et al. 2005

Eur. J. Immunol.

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Thymocyte positive and negative selection are dependent on avidity-driven TCRmediated recognition events in the thymus. High-avidity recognition events result in negative selection, while low-avidity recognition events result in positive selection. However, it has not been established how thymocytes maturation stages affect their responses to TCR signals of different avidities. We gained insight into this question when we reduced thymocyte selection to an in vitro system, in which full maturation of developmentally synchronized immature double-positive thymocytes was induced on a cloned line of thymic epithelial cells. Our analysis of the kinetics of thymocyte development supports a multi-phasic model of thymic selection. In it, thymocyte maturation stages as well as interaction avidity control the outcome TCR stimulation. Positive selection is initiated during a primary recognition event that proceeds independently of the TCR avidity. During a secondary recognition event the final fate of thymocyte, full maturation versus negative selection, is determined by TCR avidity.

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“…Immunohistochemical examinations revealed that the great majority of intraepidermal infiltrates were CD8+, and CD4+ cells were rarely seen in the cutaneous lesions. Although it seems a well established idea that CD8+ cells selectively respond to MHC class I antigens (review by Swain, 1983), there have been several reports of MHC class IIreactive CD8+ T cell clones (Haas & von Boehmer, 1984;Golding & Singer, 1985;Shinohara & Kojima, 1984). The functions of MHC class II-reactive CD8+ cells in vivo are still unknown.…”

Section: Discussionmentioning

confidence: 99%

Induction of cutaneousgraft-versus-hostdisease by local injection of unprimed T cells

Kawai

Matsumoto

Watanabe

et al. 1991

Clinical and Experimental Immunology

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SUMMARYThe skin is a major target organ in human graft-versus-host disease (GVHD) after bone-marrow transplantation. GVHD can be induced in mice by i.v. injection of T cells into unirradiated semiallogeneic or lethally irradiated allogeneic recipients. However, in the murine systemic GVHD model, cutaneous lesions occur only in lethally irradiated recipients. Since lethal irradiation itself might induce the epidermal cell damage, several investigators have employed another murine model of cutaneous GVHD, in which cutaneous lesions were induced by intradermal injection of alloreactive T cell clones. Using this system, it has been reported that both MHC class I-and IIreactive T cell clones can induce cutaneous GVHD in non-irradiated or sublethally irradiated recipients. However, it has remained unknown whether or not freshly prepared T cells are able to induce cutaneous GVHD after local injection into non-irradiated recipients. We show that unprimed T cells can induce cutaneous GVHD after local injection into unirradiated MHC class II-or I + IIdisparate recipients. In contrast to alloreactive T cell clones, unprimed T cells could elicit only mild cutaneous lesions in MHC class I-disparate recipients. Since sublethal irradiation of MHC class Idisparate recipients did not result in the manifestation of cutaneous lesions after injection of unprimed T cells, host anti-donor responses by radiosensitive cells could not be responsible for this phenomenon. This experimental system provides a useful model for analysis of the regulation mechanisms in the induction of GVHD by unprimed T cells.

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Surface markers of cytotoxic T lymphocyte clones

Abstract: Several class II major histocompatibility complex antigen-specific murine cytolytic T cell clones express Lyt-2 but not MT4 surface antigens.

Cited by 16 publications

References 13 publications

Involvement of Lyt-2 and L3T4 in activation of hapten-specific Lyt-2+ L3T4+ T-cell clones.

Involvement of Lyt-2 and L3T4 in activation of hapten-specific Lyt-2+ L3T4+ T-cell clones.

Maturational stage-dependent thymocyte responses to TCR engagement

Induction of cutaneousgraft-versus-hostdisease by local injection of unprimed T cells

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