Lyt-2 and lyt-3 antigens are on two different polypeptide subunits linked by disulfide bonds. Relationship of subunits to T cell cytolytic activity.

Ledbetter, Jeffrey A.; Seaman, William E.; Tsu, Theta T.; Herzenberg, Leonard A.

doi:10.1084/jem.153.6.1503

Cited by 139 publications

(64 citation statements)

References 25 publications

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“…Unlike blocking by anti-LFA-1, however, which affects T cells recognizing H-2 class I and class II antigens, sensitivity to inhibition by anti-Lyt-2 is considered a property of only class I-specific T cells (3). The idea that the Lyt-2-bearing molecule is itself the T cell receptor had to be discarded with the discovery ofcodominant expression of both Lyt-2 alleles on the same cell (22). Instead, it has been proposed that Lyt-2 is part of the T cell receptor complex, where it functions as a MHC classspecific receptor by interacting with monomorphic determinants on class I molecules (3).…”

Section: Blocking Of Ldcc Mediated By Polyclonally Induced Ctl With Amentioning

confidence: 99%

Monoclonal anti-Lyt-2.2 antibody blocks lectin-dependent cellular cytotoxicity of H-2-negative target cells.

Hünig¹

1984

The Journal of Experimental Medicine

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During the past years, a number of T cell antigens defined by conventional serology and monoclonal antibodies have become the basis for the distinction of T cell subsets, especially in the human, murine, and rat systems (reviewed in reference 1). Some of these markers have been directly correlated with T cell functions, either because they are only expressed on a given functional subset or because antibodies to them block or stimulate certain T cell reactions. A well studied example is the murine Lyt-2 (human OKT8/Leu-2) antigen. Originally thought to be a marker for cytotoxic (and suppressor) T cells (2), more recent data suggest an association of this antigen with T cell recognition of class I major histocompatibility complex (MHC) 1 antigens rather than with cytolytic function (3). Thus, Class I-specific helper T cells were found to be Lyt-2 + as well (4), and conversely, class II specific cytolytic T lymphocytes (CTL) with little or no Lyt-2 antigen were described (5). In the human, an analogous antigen is known to be associated with the recognition of class II MHC antigens (OKT4/Leu-3) (6, 7), and its likely murine counterpart (L3T4) has been described recently (8). The strongest evidence for an involvement of the molecules bearing these antigens in the recognition of MHC restriction elements is the capacity of antiLyt-2 (3) and anti-L3T4 (8) antibodies (and their counterparts in the human system [9]) to block the activities of cytotoxic and helper T cells that recognize class I and class II antigens, respectively. Accordingly, it has been proposed that the T cell structures defined by these antibodies interact with monomorphic determinants on MHC molecules, thereby providing an MHC class-specific recognition step in addition to the T cell receptors' interaction with its target antigen (3).Recently, evidence has been presented suggesting that the mechanism by which lectins polyclonally activate T cells (10) and mediate nonspecific (CTL)-lysis (1 1) (lectin-dependent cellular cytotoxicity, LDCC) is similar or identical to that operating in antigen-specific systems. Thus, it has been postulated that T ceils recognize lectin-modified MHC antigens on "accessory" and target cells. The finding that LDCC (12) and lectin-induced reactivity to interleukin 2 (IL-2) This work was supported by Sonderforschungsbereich 105, Wfirzburg. 1 Abbreviations used in this paper: CTL, cytotoxic T lymphocytes; Con A, concanavalin A; IL-2, interleukin 2; LDCC, lectin-dependent cellular cytotoxicity; LFA, lymphocyte-function associated antigen; MHC, major histocompatibility complex; NK, natural killer cells.J. ExP. MEn.

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Section: Blocking Of Ldcc Mediated By Polyclonally Induced Ctl With Amentioning

confidence: 99%

Monoclonal anti-Lyt-2.2 antibody blocks lectin-dependent cellular cytotoxicity of H-2-negative target cells.

Hünig¹

1984

The Journal of Experimental Medicine

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“…CD8 is encoded by two distinct genes, CD8a and CD8b, and is expressed on the surface of T cells primarily as a CD8ah heterodimer (9). The Ig domain of CD8 binds to the conserved a3 domain of MHC class I molecules, whereas the cytoplasmic tail of CD8 binds the Src kinase, lck (10,11).…”

Section: Introductionmentioning

confidence: 99%

Influence of Human CD8 on Antigen Recognition by T-Cell Receptor–Transduced Cells

Lyons

Moore²,

Brasic³

et al. 2006

Cancer Research

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The CD8 coreceptor on T cells has two functions. Namely, CD8 acts to stabilize the binding of the T-cell receptor (TCR) to the peptide-MHC complex while localizing p56 lck (lck) to the TCR/CD3 complex to facilitate early signaling events. Although both functions may be critical for efficient activation of a CTL, little is known about how the structural versus signaling roles of CD8, together with the relative strength of the TCR, influences T-cell function. We have addressed these issues by introducing full-length and truncated versions of the CD8A and CD8B chains into CD8 À Jurkat cell clones expressing cloned TCRs with known antigen specificity and relative affinities. Using a combination of antigen recognition and tetramer-binding assays, we find that the intracellular lck-binding domain of CD8 is critical for enhanced T-cell activation regardless of the relative strength of the TCR. In contrast, the extracellular domain of CD8 seems to be critical for TCRs with lower affinity but not those with higher affinity. Based on our results, we conclude that there are different requirements for CD8 to enhance T-cell function depending on the strength of its TCR. (Cancer Res 2006; 66(23): 11455-61)

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“…Another observation should be mentioned, that the Lyt-2 complex of fully differentiated CTLs shows different properties than those of thymocytes-i.e., in the reduced state only one diffuse chain of 38,000 daltons could be found for both G4 and B10 (Fig. 6) while thymocytes have subunits of -38,000 and 32,000 daltons (18,19 …”

mentioning

confidence: 99%

Monoclonal antibodies specific for a murine cytotoxic T-lymphocyte clone.

Staerz

Pasternack

Klein

et al. 1984

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

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Two antibody-secreting murine hybridomas, F1G3.1 and F2A11.5, have been established from B1O.D2 mice immunized with cells from the murine cytotoxic T-lymphocyte clone G4. The two clones used, G4 and B10, were derived from BALB.B (H-2b) mice and the target antigen specificity of both maps to the Dd region of the murine H-2 complex. However, B10 has a lower affinity for the target cells, as shown by its lower specific killing of blasts and its higher susceptibility to blocking by anti-Lyt-2 monoclonal antibody 53-6.75. The monoclonal antibodies, FlG3.1 and F2A11.5, react only with cells from clone G4. Similarly, they block only the specific cytolysis mediated by G4; no effect on cytotoxicity mediated by B10 or by heterogeneous populations of cytotoxic T lymphocytes was found. FlG3.1, especially, is very active in stimulating G4 to secrete immune interferon; B10 in contrast did not show any induction on treatment with these monoclonal antibodies. The structure of the surface antigen on G4 cells recognized by these monoclonal antibodies was revealed by immunoprecipitation studies of radioiodinated cell surface proteins. A protein dimer could be identified with an apparent molecular size of 80,000 daltons consisting of monomers migrating as 42,000-dalton proteins on reduction. So far, electrophoresis in the presence of NaDodSO4 does not indicate any heterogeneity in the size of the monomers. This molecule can be distinguished from the Lyt-2 complex.Recent reports from a number of laboratories indicate a consensus of opinion on a candidate for the T-cell antigen receptor. These reports describe similar approaches using monoclonal antibodies generated against cloned T-cell lines. The derived antibodies react only with the T cells used as immunogen. Allison et al.(1) reported a monoclonal antibody specific for a murine radiation-induced T-cell lymphoma of unknown antigen specificity and function. Meuer et al. (2) immunized mice with a human cytotoxic T-lymphocyte (CTL) clone and generated monoclonal antibodies that inhibit the specific lytic activity of the CTLs. Haskins et al. (3) described a monoclonal antibody specific for an Ia (class II)-restricted antigen-specific murine T-cell hybridoma, probably belonging to the helper T-cell lineage. In this case, the monoclonal antibody inhibited the antigen-induced secretion of interleukin 2 (IL-2). In all reports cited, the clone-specific monoclonal antibodies precipitate a surface protein of -80,000 daltons that separates into two chains of -40,000 daltons on reduction.In addition to the apparent clone-specific nature of the determinants and the ability of the antibodies to block antigenspecific function, there are other reasons to consider that the determinants recognized are idiotypes on the T-cell antigen receptor. For example, there are some comparative data suggesting microheterogeneity among the 40,000-dalton protein chains derived from different T-cell clones (4). Furthermore, it has been shown that the putative idiotypic determinant is intimately associated ...

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Lyt-2 and lyt-3 antigens are on two different polypeptide subunits linked by disulfide bonds. Relationship of subunits to T cell cytolytic activity.

Cited by 139 publications

References 25 publications

Monoclonal anti-Lyt-2.2 antibody blocks lectin-dependent cellular cytotoxicity of H-2-negative target cells.

Monoclonal anti-Lyt-2.2 antibody blocks lectin-dependent cellular cytotoxicity of H-2-negative target cells.

Influence of Human CD8 on Antigen Recognition by T-Cell Receptor–Transduced Cells

Monoclonal antibodies specific for a murine cytotoxic T-lymphocyte clone.

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