scholarly journals Private specificities of H-2K and H-2D loci as possible selective targets for effector lymphocytes in cell-mediated immunity.

1975 ◽  
Vol 141 (1) ◽  
pp. 11-26 ◽  
Author(s):  
B D Brondz ◽  
I K Egorov ◽  
G I Drizlikh
Keyword(s):  
T Lymphocytes ◽  
Target Cells ◽  
Cell Mediated Immunity ◽  
Skin Grafts ◽  
Immune Lymphocytes ◽  
Direct Cytotoxicity ◽  
Cross Absorption ◽  
Private Specificity ◽  
Two Populations

Receptors of effector T lymphocytes of congeneic strains of mice do not recognize public H-2 specificities and react to private H-2 specificities only. This has been established with the use of three tests: direct cytotoxicity assay of immune lymphocytes upon target cells, specific absorption of the lymphocytes on the target cells, and rejection of skin grafts at an accelerated fashion. Immunization with two private H-2 specificities in the system C57BL/10ScSn leads to B10.D2 induces formation of two corresponding populations of effector lymphocytes in unequal proportion: a greater part of them is directed against the private specificity H-2.33 (Kb), while the smaller part is towards H-2.2 (Db) private specificity. These two populations of effector lymphocytes do not overlap, as demonstrated by experiments on their cross-absorption on B10.D2 (R107), B10.D2 (R101), B10.A(2R), and B10.A(5R) target cells, as well as on mixtures of R107 and R101 targets. Following removal of lymphocytes reacting with one of the private H-2 specificities, lymphocytes specific to the other specificity are fully maintained. A mixture of target cells, each bearing one of the two immunizing private specificities, absorbs 100% of the immune lymphocytes and is totally destroyed by them. It is suggested that H-2 antigens are natural complexes of hapten-carrier type, in which the role of hapten is played by public H-2 specifities and that of the carrier determinant by either private H-2 specificities or structures closely linked to them. Various models of steric arrangement of MHC determinants recognized by receptors of effector T lymphocytes are discussed.

scholarly journals Role of antigen, CD8, and cytotoxic T lymphocyte (CTL) avidity in high dose antigen induction of apoptosis of effector CTL.

1996 ◽  
Vol 184 (2) ◽  
pp. 485-492 ◽  
Author(s):  
M A Alexander-Miller ◽  
G R Leggatt ◽  
A Sarin ◽  
J A Berzofsky
Keyword(s):  
T Lymphocytes ◽  
Cytotoxic T Lymphocyte ◽  
Target Cells ◽  
High Dose ◽  
High Avidity ◽  
Apoptotic Pathway ◽  
Peptide Antigen ◽  
Kinetics Of ◽  
Selection Of

Experimental data suggest that negative selection of thymocytes can occur as a result of supraoptimal antigenic stimulation. It is unknown, however, whether such mechanisms are at work in mature CD8+ T lymphocytes. Here, we show that CD8+ effector cytotoxic T lymphocytes (CTL) are susceptible to proliferative inhibition by high dose peptide antigen, leading to apoptotic death mediated by TNF-alpha release. Such inhibition is not reflected in the cytolytic potential of the CTL, since concentrations of antigen that are inhibitory for proliferation promote efficient lysis of target cells. Thus, although CTL have committed to the apoptotic pathway, the kinetics of this process are such that CTL function can occur before death of the CTL. The concentration of antigen required for inhibition is a function of the CTL avidity, in that concentrations of antigen capable of completely inhibiting high avidity CTL maximally stimulate low avidity CTL. Importantly, the inhibition can be detected in both activated and resting CTL. Blocking studies demonstrate that the CD8 molecule contributes significantly to the inhibitory signal as the addition of anti-CD8 antibody restores the proliferative response. Thus, our data support the model that mature CD8+ CTL can accommodate an activation signal of restricted intensity, which, if surpassed, results in deletion of that cell.

N-linked oligosaccharides can protect target cells from the lysis mediated by NK cells but not by cytotoxic T lymphocytes: role of NKG2-A

1999 ◽  
Vol 54 (2) ◽  
pp. 113-121 ◽  
Author(s):  
M.-A. Sol ◽  
N. Vacaresse ◽  
J. Lule ◽  
C. Davrinche ◽  
B. Gabriel ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Nk Cells ◽  
Cytotoxic T Lymphocytes ◽  
Target Cells

Target cell death triggered by cytotoxic T lymphocytes: a target cell mutant distinguishes passive pore formation and active cell suicide mechanisms

1994 ◽  
Vol 14 (1) ◽  
pp. 427-436
Author(s):  
D S Ucker ◽  
J D Wilson ◽  
L D Hebshi
Keyword(s):  
Cell Death ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Target Cell ◽  
Active Cell ◽  
Death Process ◽  
Target Cells ◽  
Antigenic Stimulus ◽  
Cell Suicide

The role of the target cell in its own death mediated by cytotoxic T lymphocytes (CTL) has been controversial. The ability of the pore-forming granule components of CTL to induce target cell death directly has been taken to suggest an essentially passive role for the target. This view of CTL-mediated killing ascribes to the target the single role of providing an antigenic stimulus to the CTL; this signal results in the vectoral degranulation and secretion of pore-forming elements onto the target. On the other hand, by a number of criteria, target cell death triggered by CTL appears fundamentally different from death resulting from membrane damage and osmotic lysis. CTL-triggered target cell death involves primary internal lesions of the target cell that reflect a physiological cell death process. Orderly nuclear disintegration, including lamin phosphorylation and solubilization, chromatin condensation, and genome digestion, are among the earliest events, preceding the loss of plasma membrane integrity. We have tested directly the involvement of the target cell in its own death by examining whether we could isolate mutants of target cells that have retained the ability to be recognized by and provide an antigenic stimulus to CTL while having lost the capacity to respond by dying. Here, we describe one such mutant, BW87. We have used this CTL-resistant mutant to analyze the mechanisms of CTL-triggered target cell death under a variety of conditions. The identification of a mutable target cell element essential for the cell death response to CTL provides genetic evidence that target cell death reflects an active cell suicide process similar to other physiological cell deaths.

scholarly journals The recombinant 65-kD heat shock protein of Mycobacterium bovis Bacillus Calmette-Guerin/M. tuberculosis is a target molecule for CD4+ cytotoxic T lymphocytes that lyse human monocytes.

1988 ◽  
Vol 168 (5) ◽  
pp. 1947-1952 ◽  
Author(s):  
T H Ottenhoff ◽  
B K Ab ◽  
J D Van Embden ◽  
J E Thole ◽  
R Kiessling
Keyword(s):  
Heat Shock ◽  
T Lymphocytes ◽  
Heat Shock Protein ◽  
Cytotoxic T Cells ◽  
Target Cells ◽  
Bacillus Calmette Guerin ◽  
Effector Cells ◽  
Intracellular Parasites ◽  
Human Immune Response

Since little is known about Tc cells in the human immune response to intracellular parasites, we have studied the role of Tc cells in response to M. bovis Bacillus Calmette-Guerin (BCG). Donors whose PBMC responded to BCG, purified protein derivative (PPD), and the recombinant 65-kD heat shock protein (HSP) of BCG generated BCG/PPD-specific CD4+ effector T lymphocytes that lysed PPD as well as recombinant 65-kD-pulsed monocytes. Nonpulsed or irrelevant antigen-pulsed target cells were lysed to a much lower but still significant extent. PPD-stimulated effector lymphocytes of a recombinant 65-kD nonresponder lysed PPD but not recombinant 65-kD-pulsed monocytes. Recombinant 65-kD-educated effector lymphocytes lysed both recombinant 65-kD- and PPD-pulsed monocytes. In addition, these effector cells efficiently lysed nonpulsed target cells. These results demonstrate that in recombinant 65-kD responders, the recombinant 65-kD HSP of BCG is an immunodominant target as well as a triggering molecule for BCG/PPD-specific CD4+ cytotoxic T cells that lyse autologous monocytes. The implications of these findings with respect to the role of the 65-kD HSP in autoimmunity are discussed.

scholarly journals Target cell death triggered by cytotoxic T lymphocytes: a target cell mutant distinguishes passive pore formation and active cell suicide mechanisms.

1994 ◽  
Vol 14 (1) ◽  
pp. 427-436 ◽  
Author(s):  
D S Ucker ◽  
J D Wilson ◽  
L D Hebshi
Keyword(s):  
Cell Death ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Target Cell ◽  
Active Cell ◽  
Death Process ◽  
Target Cells ◽  
Antigenic Stimulus ◽  
Cell Suicide

The role of the target cell in its own death mediated by cytotoxic T lymphocytes (CTL) has been controversial. The ability of the pore-forming granule components of CTL to induce target cell death directly has been taken to suggest an essentially passive role for the target. This view of CTL-mediated killing ascribes to the target the single role of providing an antigenic stimulus to the CTL; this signal results in the vectoral degranulation and secretion of pore-forming elements onto the target. On the other hand, by a number of criteria, target cell death triggered by CTL appears fundamentally different from death resulting from membrane damage and osmotic lysis. CTL-triggered target cell death involves primary internal lesions of the target cell that reflect a physiological cell death process. Orderly nuclear disintegration, including lamin phosphorylation and solubilization, chromatin condensation, and genome digestion, are among the earliest events, preceding the loss of plasma membrane integrity. We have tested directly the involvement of the target cell in its own death by examining whether we could isolate mutants of target cells that have retained the ability to be recognized by and provide an antigenic stimulus to CTL while having lost the capacity to respond by dying. Here, we describe one such mutant, BW87. We have used this CTL-resistant mutant to analyze the mechanisms of CTL-triggered target cell death under a variety of conditions. The identification of a mutable target cell element essential for the cell death response to CTL provides genetic evidence that target cell death reflects an active cell suicide process similar to other physiological cell deaths.

The role of E receptors in the attachment of thymocytes and T lymphocytes to human target cells

1983 ◽  
Vol 29 (3) ◽  
pp. 349-358 ◽  
Author(s):  
M. Schlesinger ◽  
J. Levy ◽  
R. Laskov ◽  
R. Hadar ◽  
J. Weinstock ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Target Cells

scholarly journals Clonal heterogeneity in the functional requirement for Lyt-2/3 molecules on cytolytic T lymphocytes: analysis by antibody blocking and selective trypsinization.

1982 ◽  
Vol 156 (6) ◽  
pp. 1711-1722 ◽  
Author(s):  
H R MacDonald ◽  
A L Glasebrook ◽  
J C Cerottini
Keyword(s):  
T Lymphocytes ◽  
Direct Evidence ◽  
Cross Reactivity ◽  
Cytolytic Activity ◽  
Antigenic Determinants ◽  
Target Cells ◽  
Cytolytic T Lymphocytes ◽  
Clonal Heterogeneity ◽  
Flow Microfluorometry

While it is well established that murine cytolytic T lymphocytes (CTL) express the Lyt-2/3 molecular complex on their surface, conflicting results have been reported concerning the role of this complex in CTL activity. In the present study this question was reinvestigated at the clonal level. Although different (H-2b anti-H-2d) CTL clones expressed comparable amounts of Lyt-2/3 molecules, as assessed by quantitative flow microfluorometry, the activity of some clones was inhibited by low doses (10 ng) of monoclonal anti-Lyt-2 or anti-Lyt-3 antibodies (in the absence of complement), whereas other clones were not inhibited by either antibody at doses as high as 5 microgram. Treatment of these clones with doses of trypsin sufficient to cleave Lyt-2/3 antigenic determinants from the cell surface resulted in a similar dissociation: clones that were inhibited by antibodies lost cytolytic activity, whereas "uninhibited" clones were unaffected by trypsin treatment. Moreover, the dissociation observed among different alloreactive clones could be demonstrated with self-H-2-restricted (H-2b anti-MSV) clones exhibiting cross-reactivity with normal H-2d products. The lytic activity of these clones against the relevant syngeneic target cells was unaffected by anti-Lyt-2 antibodies or trypsin, whereas their cross-reactivity on H-2d target cells was abolished by either treatment. These results provide direct evidence for clonal heterogeneity in the requirement for Lyt-2/3 molecules in CTL-mediated lysis. It is proposed that the function of Lyt-2/3 molecules is to stabilize the interaction between CTL receptors and the corresponding antigens on the target cells and that the requirement for such a stabilization is correlated with low number and/or affinity of CTL receptors.

Sign in / Sign up

Export Citation Format

Share Document