Molecular Interactions in T‐Cell‐Mediated Cytotoxicity

Bonavida, Benjamin; Bradley, Thomas; Fan, John; Hiserodt, John C.; Effros, Rita B.; Wexler, Hannah M.

doi:10.1111/j.1600-065x.1983.tb01075.x

Cited by 22 publications

(7 citation statements)

References 35 publications

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“…As shown in Table 6, a similar asymmetry is also observed in the activation of resting T cells by Con A pulsing of T cells or AC, where at least "self-destruction" is not a likely mechanism for the inactivation of T cells. On the other hand, experiments performed both in oxidation-mediated T cell killing [28] and in the activation of resting T cells ( [25,271 and this publication) show that pretreatment of either partner is equally effective (see above). The difference between the lectin and oxidation-mediated systems remains, therefore, to be resolved.…”

Section: Discussionmentioning

confidence: 90%

“…Thus, the Schiff bases that form between the enzymatically created aldehyde groups and free amino groups on other proteins seem to act by cross-linking cells [24] and not by cross-linking surface structures (including H-2 antigens) on the AC which are then recognized as foreign by the T cells. Recent experiments performed in oxidation-dependent nonspecific lysis of target cells by CTL have produced corresponding results [28]. The formation of intercellular Schiff bases has been visualized in preliminary experiments in which proteins from surface-labeled T cells coincubated with oxidized B cell blasts were immunoprecipitated from detergent extracts of this cell mixture with antibodies to B cell surface proteins (not shown).…”

Section: Discussionmentioning

confidence: 92%

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The role of accessory cells in polyclonal T cell activation III. No requirement for recognition of H‐2‐encoded antigens on accessory cells

Hünig

1984

Eur J Immunol

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Highly purified murine lymph node T cells were used to test the hypothesis that polyclonal T cell activation requires the recognition of mitogen-modified major histocompatibility complex (MHC) antigens on accessory cells (AC) by the T cells. A variety of tumor cells lines, including macrophage, B and mast cell tumors, as well as thymomas, were shown to function as AC in concanavalin A-induced T cell activation, even if they expressed only one class of MHC antigens or none at all. In contrast to antigen-specific responses, where the Lyt-2+ phenotype is reportedly associated with recognition of class I MHC antigens, T cells enriched for or depleted of Lyt-2+ cells were not preferentially activated in the presence of class I- or class II-positive AC, respectively. In addition, as shown by others in the guinea pig and in the rat systems, T cell proliferation induced by oxidation of cell surface sugars is equally effective if T cells or AC are oxidized. T cell mitogens, therefore, do not seem to act by altering MHC antigens on AC, but rather by providing T cell-AC contact via their agglutinating properties.

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 92%

The role of accessory cells in polyclonal T cell activation III. No requirement for recognition of H‐2‐encoded antigens on accessory cells

Hünig

1984

Eur J Immunol

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“…As recently as 1983, a volume of Immunological Reviews ("Mechanism [72], demonstrated the various views of workers in this field.…”

Section: Assembly Of Cytolytic Complexes By Ctl and Nk Lymphocytes Inmentioning

confidence: 97%

Molecular mechanisms of cytolysis by complement and by cytolytic lymphocytes

Podack

1986

J of Cellular Biochemistry

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Recent advances in our understanding of the mechanism of NK cell and cytolytic Tlymphocyte (CTL)-mediated cytolysis have revealed intriguing analogies of lymphocytic effector mechanisms with those of complement. Each of these cytolytic effector systems assembles on target membranes cytolytically active, tubular complexes from hydrophilic precursor proteins. Membrane insertion of the tubular complexes gives rise to ultrastructural membrane lesions and causes target cell lysis by disruption of the target membrane ( Fig. 1). Assembly of tubular transmembrane complexes involves the polymerization of monomeric precursor proteins to transmembrane pores that serve to lyse cells directly and to permit entry of additional lytic factors. This review will summarize the molecular events resulting in the formation of membrane lesions by lymphocytes and by complement and our knowledge of additional cytolytic factors. It will become apparent that there are striking analogies in the morphology and function of the tubular complexes, their mode of assembly, as well as their utilization as transmembrane channels for entry of cytolytic factors. ASSEMBLY OF THE MEMBRANE ATTACK COMPLEX (MAC) OF COMPLEMENTFormation of the MAC proceeds in a stepwise assembly of five proteins to a complex with approximately 20 subunits. The assembly may be divided into two stages with regard to function, structure, and control: (1) The insertional event carried out by the trimolecular C5b-7 complex. This reaction proceeds without overt lysis but it sets the stage for subsequent membrane damage. (2) Membrane damage by binding of C8 and polymerization of C9 to the tubular transmembrane complex that is responsible for formation of the ultrastructural membrane lesion.For the purpose of this review, the second stage, the formation of membrane lesions by polymerization of C9, will be described first because it exemplifies

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“…Basically, two functions have been suggested for the Lyt-2 bearing T-cell surface molecule: strengthening of adhesion between CTL and target cell (12,20), and recognition of class I MHC antigens (3). Both proposals take into account that inhibition of cytolysis by anti-Lyt-2 antibodies operates at the level of CTL-target cell conjugate formation (21).…”

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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Molecular Interactions in T‐Cell‐Mediated Cytotoxicity

Cited by 22 publications

References 35 publications

The role of accessory cells in polyclonal T cell activation III. No requirement for recognition of H‐2‐encoded antigens on accessory cells

The role of accessory cells in polyclonal T cell activation III. No requirement for recognition of H‐2‐encoded antigens on accessory cells

Molecular mechanisms of cytolysis by complement and by cytolytic lymphocytes

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

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