scholarly journals The calcium-binding protein calreticulin is a major constituent of lytic granules in cytolytic T lymphocytes.

1993 ◽  
Vol 177 (1) ◽  
pp. 1-7 ◽  
Author(s):  
M Dupuis ◽  
E Schaerer ◽  
K H Krause ◽  
J Tschopp
Keyword(s):  
T Lymphocytes ◽  
Calcium Binding ◽  
Secretory Granules ◽  
Cell Receptor ◽  
Lak Cells ◽  
Major Constituent ◽  
Target Cells ◽  
Cytolytic T Lymphocytes ◽  
Lytic Granules ◽  
Associated Proteins

Cytolytic T lymphocytes (CTL), natural killer cells, and lymphokine-activated killer (LAK) cells are cytolytic cells known to release the cytolytic protein perforin and a family of proteases, named granzymes, from cytoplasmic stores upon interaction with target cells. We now report the purification of an additional major 60-kD granule-associated protein (grp 60) from human LAK cells and from mouse cytolytic T cells. The NH2-terminal amino acid sequence of the polypeptide was found to be identical to calreticulin. Calreticulin is a calcium storage protein and carries a COOH-terminal KDEL sequence, known to act as a retention signal for proteins destined to the lumen of the endoplasmic reticulum. In CTLs, however, calreticulin colocalizes with the lytic perforin to the lysosome-like secretory granules, as confirmed by double label immunofluorescence confocal microscopy. Moreover, when the release of granule-associated proteins was triggered by stimulation of the T cell receptor complex, calreticulin was released along with granzymes A and D. Since perforin is activated and becomes lytic in the presence of calcium, we propose that the role of calreticulin is to prevent organelle autolysis due to the protein's calcium chelator capacity.

scholarly journals Specificity studies on cytolytic T lymphocytes directed against murine leukemia virus-induced tumors. Analysis of monoclonal cytolytic T lymphocytes.

1982 ◽  
Vol 155 (4) ◽  
pp. 1050-1062 ◽  
Author(s):  
F Plata
Keyword(s):  
T Lymphocytes ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Target Cells ◽  
Cytolytic T Lymphocytes ◽  
Tumor Target ◽  
Induced Tumors ◽  
Definition Of ◽  
Leukemia Viruses ◽  
Murine Leukemia

The specificities of cloned cytolytic T lymphocytes (CTL) were studied for the analysis of CTL populations generated against murine leukemia viruses (MuLV) in H-2 congenic BALB/c (H-2d) and BALB.B (H-2b) mice. In particular, CTL generated in response to tumors induced by Gross MuLV and Friend MuLV were studied; these tumors expressed virus-induced antigens that do not cross-react and that can be distinguished from each other. The systematic study of 92 CTL clones clearly indicated that MuLV-immune CTL were highly heterogeneous with respect to both the intensities of target cell lysis that they mediated and to their specificity of recognition of MuLV-induced tumor target cells. Various categories of CTL clones were identified, ranging from CTL clones tht were tightly H-2 restricted and specific for the immunizing tumor to CTL clones that displayed no discernible patterns of specificity and that attacked a large number of different target cells. In addition, the surface markers of these cloned CTL were defined, and the best conditions for their prolonged maintenance in culture were determined. The present data indicate that future efforts in the definition of target antigens recognized by tumor-specific CTL should be performed with monoclonal lymphocytes.

Ultrastructure of conjugates of cytolytic T lymphocytes and target cells

1978 ◽  
Vol 85 (5) ◽  
pp. 611-616
Author(s):  
S. N. Bykovskaya ◽  
M. O. Raushenbakh ◽  
A. N. Rytenko ◽  
A. F. Bykovskii
Keyword(s):  
T Lymphocytes ◽  
Target Cells ◽  
Cytolytic T Lymphocytes

scholarly journals Primary generation of cytolytic T lymphocytes in the absence of DNA synthesis.

1979 ◽  
Vol 150 (1) ◽  
pp. 196-201 ◽  
Author(s):  
H R MacDonald ◽  
R K Less
Keyword(s):  
T Lymphocytes ◽  
Dna Synthesis ◽  
Cytolytic Activity ◽  
Target Cells ◽  
Cytolytic T Lymphocytes ◽  
Spleen Cells ◽  
Con A ◽  
A Cell ◽  
Stimulation Of

The requirement for DNA synthesis during the primary differentiation of cytolytic T lymphocytes (CTL) had been investigated. CTL were induced polyclonally in vitro by stimulation of normal C57BL/6 spleen cells with concanavalin A (Con A)and their cytolytic activity was tested against 51Cr-labeled target cells in the presence of Bacto Phytohemagglutinin M. With this system, CTL activity could first be detected 48 h after exposure of spleen cells to Con A. Addition of cytosine arabinoside at concentrations sufficient to reduce DNA synthesis by 95-98% in Con A-stimulated cultures did not significantly inhibit the generation of cytolytic activity on a cell-to-cell basis. These results demonstrate that derepression of the genetic information required for the expression of CTL function can occur in the absence of detectable DNA synthesis.

scholarly journals Characterization of CD3+, CD4-, CD8- clones expressing the putative T cell receptor gamma gene product. Analysis of the activation pathways leading to interleukin 2 production and triggering of the lytic machinery.

1987 ◽  
Vol 166 (1) ◽  
pp. 277-282 ◽  
Author(s):  
S Ferrini ◽  
C Bottino ◽  
R Biassoni ◽  
A Poggi ◽  
R P Sekaly ◽  
...  
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
T Cell Receptor ◽  
Cell Activation ◽  
Human Peripheral Blood ◽  
Interleukin 2 ◽  
Cell Receptor ◽  
Target Cells ◽  
Product Analysis ◽  
Alpha Beta

Four clones were derived from human peripheral blood T lymphocytes from which CD4+ and CD8+ cells had been removed by treatment with specific mAbs and complement. All expressed the CD2+, 3+, 4-, 8-, T44- phenotype, and did not react with the WT31 mAb, which is specific for a framework determinant of the CD3-associated alpha/beta heterodimer which serves as receptor for antigen on most human T lymphocytes. Surface iodination followed by crosslinking with dithiobis-succinimidyl propionate (DSP) and immunoprecipitation with anti-CD3 mAbs indicated that, in all four clones, the CD3-associated molecules consisted of a major 45 kD band and a minor band of 43 kD. Northern blot analysis showed that mRNA for the gamma chain was expressed at high levels, whereas mRNA for the alpha chain was missing; beta chain mRNA was present in a defective form (1 kb instead of 1.3 kb). These data support the concept that these clones may express, in association with CD3, the molecular product of the T cell receptor gamma genes instead of the typical alpha/beta heterodimer. CD3+, WT31- clones lysed the NK-sensitive K562 target cells and produced IL-2 upon stimulation with PHA. In addition, they released IL-2 after triggering with soluble anti-CD3 mAbs or with an appropriate combination of anti-CD2 mAbs (in the presence of adherent cells). When CD3+, WT31- clones were incubated with an anti-CD3 producing hybridoma as triggering target, the latter was efficiently lysed. Target cell lysis also occurred when a suitable combination of anti-CD2 mAbs-producing hybridomas was used. Therefore, CD3+, WT31- cells appear to use two pathways of cell activation that function also in conventional CD3+, WT31+ T cells, but they lack a third putative pathway initiated by T44 surface molecules.

scholarly journals Recognition of viral glycoproteins by influenza A-specific cross-reactive cytolytic T lymphocytes.

1980 ◽  
Vol 151 (4) ◽  
pp. 945-958 ◽  
Author(s):  
U H Koszinowski ◽  
H Allen ◽  
M J Gething ◽  
M D Waterfield ◽  
H D Klenk
Keyword(s):  
T Lymphocytes ◽  
Influenza A ◽  
Type A ◽  
Lipid Vesicles ◽  
Influenza Viruses ◽  
M Protein ◽  
Antigenic Determinants ◽  
Target Cells ◽  
Cytolytic T Lymphocytes ◽  
Viral Glycoproteins

Two populations of cytolytic T lymphocytes (CTL) generated after influenza A virus infection can be distinguished into one with specificity for the sensitizing hemagglutinin type and a second with cross-reactivity for antigens induced by other type-A influenza viruses. The molecules carrying the antigenic determinants recognized by the cross-reactive CTL were studied. In L-929 cells abortively infected with fowl plague virus, matrix (M) protein synthesis is specifically inhibited, whereas the envelope glycoproteins, hemagglutinin and neuraminidase, are synthesized and incorporated into the plasma membrane. These target cells were lysed by cross-reactive CTL. The envelope proteins of type A/Victoria virus were separated from the other virion components and reconstituted into lipid vesicles that lacked M protein that subsequently were used to prepare artificial target cells. Target-cell formation with vesicles was achieved by addition of fusion-active Sendai virus. These artificial target cells were also susceptible to lysis by cross-reactive CTL. In contrast to previous observations that suggested that the M protein of influenza viruses is recognized by these effector cells, we present evidence that the antigencic determinants induced by the viral glycoproteins are recognized.

scholarly journals Antigen recognition by H-2-restricted cytolytic T lymphocytes is not mediated by two independent receptors.

1984 ◽  
Vol 159 (1) ◽  
pp. 330-335 ◽  
Author(s):  
D T Harris ◽  
H R MacDonald ◽  
J C Cerottini
Keyword(s):  
T Lymphocytes ◽  
Sendai Virus ◽  
Leukemia Virus ◽  
Antigen Recognition ◽  
Target Cells ◽  
Cytolytic T Lymphocytes ◽  
Antigen Receptors ◽  
Nominal Antigen ◽  
Moloney Leukemia Virus ◽  
Fusion Products

Detergent-solubilized murine cytolytic T lymphocytes (CTL) clones were incorporated into Sendai virus-containing synthetic liposomes. When these liposomes were then fused with other CTL clones possessing a different non-cross-reacting specificity, the fusion products were observed to lyse target cells recognized by both parental CTL clones. This method was then used with two H-2-restricted CTL clones of different, non-cross-reacting specificities (anti-H-2b-H-Y or anti-H-2b Moloney leukemia virus). Once again, the fusion products were found to be lytic against both target cells recognized by the parental clones, but in no instance was there any observable lysis of target cells bearing the same nominal antigen in the context of different H-2 molecules. These results provide strong evidence that antigen recognition by H-2-restricted CTL is not mediated by two independent antigen receptors.

Mitogen-induced blast cells of C type virus-infected mice as target cells for cytolytic T lymphocytes

1980 ◽  
Vol 37 (3-4) ◽  
pp. 249-260 ◽  
Author(s):  
Véronique Duprez ◽  
Yvette Hénin ◽  
Jean-Paul Lévy
Keyword(s):  
T Lymphocytes ◽  
Target Cells ◽  
Type Virus ◽  
Cytolytic T Lymphocytes ◽  
Blast Cells

scholarly journals Cross-reactive lysis of trinitrophenyl (TNP)-derivatized H-2 incompatible target cells by cytolytic T lymphocytes generated against syngeneic TNP spleen cells.

1976 ◽  
Vol 144 (6) ◽  
pp. 1609-1620 ◽  
Author(s):  
S J Burakoff ◽  
R N Germain ◽  
B Benacerraf
Keyword(s):  
T Lymphocytes ◽  
Red Blood Cells ◽  
Target Cell ◽  
Blood Cells ◽  
Surface Antigens ◽  
Lymphoid Cells ◽  
Target Cells ◽  
Cytolytic T Lymphocytes ◽  
Spleen Cells ◽  
Normal Spleen

Normal spleen cells, when cultured with irradiated trinitrophenyl (TNP)-derivatized syngeneic spleen cells, develop cytotoxic effectors that lyse most effectiviely a TNP-derivatized target that is H-2 compatible with the effector. However, these effectors also lyse to a lesser extent TNP tumor and TNP spleen targets that are H-2 incompatible. This cross-reactive lysis correlates with the degree of cytolysis seen on the TNP-derivatized syngeneic target; it appears to be medicated by Thy 1.2-bearing cells and is inhibited by antisera to the K and/or D loci of the target cell and not by antisera to non-K or non-D surface antigens. Nonradiolabeled TNP-derivatized lymphoid cells syngeneic to either the stimulator or the target are able to competitively inhibit cross-reactive lysis, while TNP chicken red blood cells are unable to specifically inhibit lysis. These data on cross-reactive lysis of TNP-conjugated targets are most consistent with the altered-self hypothesis.

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