scholarly journals Regulation of T-cell-mediated lympholysis by the murine major histocompatibility complex. I. Preferential in vitro responses to trinitrophenyl-modified self K- and D-coded gene products in parental and F1 hybrid mouse strains.

1979 ◽  
Vol 149 (6) ◽  
pp. 1379-1392 ◽  
Author(s):  
R B Levy ◽  
G M Shearer
Keyword(s):  
T Cell ◽  
T Cell Response ◽  
Mouse Strains ◽  
Response Patterns ◽  
Spleen Cells ◽  
F1 Hybrid ◽  
Ctl Response ◽  
Histocompatibility Complex ◽  
D Region

Spleen cells from H-2b,k,d C57Bl/10 congenic mice were sensitized in vitro to trinitrobenzenesulfonate (TNBS)-modified autologous spleen cells. Cold target competition studies at the lytic phase demonstrated three distinct patterns of cytotoxic responsiveness: (a) H-2b spleen cells generated approximately equivalent CTL responses against Kb and Db modified self products, (b) H-2d spleen cells generated preferential responses against Dd modified self products, and (c) H-2k spleen cells generated cytotoxic responses which could only be detected against Kk self products in association with TNP. F1 spleen cells were sensitized against autologous TNBS-treated cells. The results showed that, although H-2b parental cells generated approximately equivalent Kb-TNP- and Db-TNP-specific CTL, the presence of the H-2b haplotype did not result in the generation of (a) Dk-TNP CTL response by (H-2b x H-2k) spleen cells, nor (b) a Db CTL response by (H-2b x H-2a) F1 spleen cells. Additionally, (H-2d x H-2k) F1 cells failed to generate detectable Dd-TNP-specific CTL, although H-2d parental cells generated D-regional-specific CTL. The findings demonstrated that these F1 response patterns paralleled those of the H-2k and H-2a parents, i.e. weak or no D-region TNP-specific CTL were induced. Because (H-2d x H-2a) F1 responders stimulated with H-2d TNBS-treated cells did generate good Dd TNP responses, the results illustrated that the presence of responder genes was not sufficient to result in a D-region TNP CML. It is suggested that the absence of Kk alleles on the stimulating population is necessary for the generation of D-region TNP CTL in these F1's. Mechanisms which could account for these response patterns in parental F1 mice are discussed including immunodominance, suppression, T-cell response , and Ir-gene defects.

scholarly journals Antigen recognition by a T cell clone outside the context of the major histocompatibility complex. A role for Mls in antigen presentation.

1984 ◽  
Vol 159 (1) ◽  
pp. 305-312 ◽  
Author(s):  
S J Waters ◽  
S D Waksal ◽  
G P Norton ◽  
C A Bona
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
Cell Clone ◽  
Antigen Recognition ◽  
Major Histocompatibility ◽  
Spleen Cells ◽  
Differentiation Markers ◽  
Histocompatibility Complex ◽  
T Cell Clone

A T cell clone isolated from antigen-primed CB6/F1 mice was shown to proliferate to keyhole limpet hemocyanin (KLH) in the presence of irradiated syngeneic F1 spleen cells, as well as spleen cells from either parental strain (BALB/c and C57BL/6). The genetic restriction involved in this antigen-specific proliferation was mapped using BXD (C57BL/6 X DBA/2) recombinant inbred strains of mice to the Mls gene on chromosome one. To exclude the role of Ia antigens as the restricting determinants, monoclonal anti-Ia antibodies were used to block the in vitro proliferative response of this clone. Although anti-Iab and anti-Iad blocked the proliferation of this clone to KLH in the presence of irradiated spleen cells from either parent, this effect was shown to be dependent on Ia molecules passively absorbed by the T cell clone from the irradiated filler cells. Since the T clone expressed Thy-1.2 and Lyt-1+ differentiation markers, its helper activity was compared with other KLH carrier-specific clones in an in vitro antibody synthesis assay. The Mls-KLH-restricted T cell clone, in contrast to other carrier-specific, major histocompatibility complex (MHC)-restricted T cell clones, was unable to cooperate with trinitrophenyl (TNP)-primed B cells in the presence of TNP-KLH to generate an anti-TNP response. These experiments suggest that non-MHC determinants, such as autologous Mls gene products, may play a role in genetically restricted antigen recognition by T lymphocytes.

scholarly journals Protection against graft vs. host-associated immunosuppression in F1 mice. I. Activation of F1 regulatory cells by host-specific anti-major histocompatibility complex antibodies.

1981 ◽  
Vol 154 (6) ◽  
pp. 1922-1934 ◽  
Author(s):  
U Hurtenbach ◽  
D H Sachs ◽  
G M Shearer
Keyword(s):  
Major Histocompatibility Complex ◽  
Cytotoxic T Lymphocyte ◽  
Major Histocompatibility ◽  
Spleen Cells ◽  
Cell Surface Antigens ◽  
F1 Hybrid ◽  
Histocompatibility Complex ◽  
Parental Haplotype ◽  
Ctl Responses

Injection of parental spleen cells into unirradiated F1 hybrid mice results in suppression of the potential to generate cytotoxic T lymphocyte (CTL) responses in vitro. In an attempt to protect the F1 mice from immunosuppression, the recipients were injected with antibodies specific for major histocompatibility complex (MHC)-encoded antigens of the F1 mice 24 h before inoculation of the parental spleen cells. 8-14 d later, the generation of CTL responses in vitro against H-2 alloantigens was tested. Alloantiserum directed against either parental haplotype of the F1 strain markedly diminished the suppression of CTL activity. Furthermore, monoclonal antibodies recognizing H-2 or Ia antigens protected the F2 mice from parental spleen cell-induced suppression. Although this study has been limited to reagents that recognize host H-2 determinants, these findings do not necessarily imply that protection against graft vs. host (GvH) can be achieved only with anti-MHC antibodies. However, protection was observed only by antibodies reactive with F1 antigens, and small amounts of the alloantibodies were sufficient to diminish CTL suppression. Adoptive transfer of spleen cells from syngeneic F1 mice treated with anti-h-2a alloantiserum 24 h previously provided protection equal to that of injection of the recipients with alloantibodies. The cells necessary for this effect were shown to be T cells and to be radiosensitive to 2000 rad. This cell population is induced by antisera against F1 cell surface antigens and effectively counteracts GvH-associated immuno-suppression.

scholarly journals T cell determinant structure: cores and determinant envelopes in three mouse major histocompatibility complex haplotypes.

1991 ◽  
Vol 173 (3) ◽  
pp. 609-617 ◽  
Author(s):  
G Gammon ◽  
H M Geysen ◽  
R J Apple ◽  
E Pickett ◽  
M Palmer ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
T Cell Response ◽  
Single Amino Acid ◽  
Foreign Protein ◽  
Antigenic Determinants ◽  
Mouse Strains ◽  
Major Histocompatibility ◽  
Mouse Major Histocompatibility Complex ◽  
Histocompatibility Complex

T lymphocytes recognize discrete regions on an antigen. The specificity of the T cell responses in three mouse strains of differing major histocompatibility complex (MHC) haplotype to a protein antigen, lysozyme, was analyzed using a series of peptides that walk the antigen in single amino acid steps. These peptide series were synthesized using the pin synthesis system, which was modified to allow the peptides to be cleaved from the pins into a physiological buffer free of toxic compounds. This methodology overcomes many of the problems associated with the production of peptides for screening proteins for antigenic determinants. The T cell determinants for the three strains were markedly different. This result points out the limitations of algorithms predicting determinants without reference to the MHC, and the importance of the empirical methodology. This analysis of the T cell response to lysozyme constitutes the most complete study of reactivity to a foreign protein to date and illustrates many important features of antigen recognition by T cells, e.g., presence of major and minor determinant regions. The outer boundaries of each immunogenic region, the determinant envelope, are difficult to define from recently immunized lymph nodes because of the heterogeneity in T cell recognition. However, core sequences common to all the immunogenic peptides in a continuous sequence can be easily defined.

scholarly journals Primary in vitro cytotoxic T cell response to non-major histocompatibility complex alloantigens in normal mice.

1982 ◽  
Vol 156 (2) ◽  
pp. 610-621 ◽  
Author(s):  
S Macphail ◽  
I Yron ◽  
O Stutman
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
Calf Serum ◽  
Suppressor Cells ◽  
T Cell Response ◽  
Cytotoxic T Cell ◽  
Mouse Serum ◽  
Major Histocompatibility ◽  
Histocompatibility Complex

We have shown for the first time that it is possible to consistently generate a primary in vitro cytotoxic T cell (Tc) response to non-major histocompatibility complex alloantigens using responder cells from a normal mouse strain. This was achieved by carrying out, in the generating phase, a limiting dilution procedure in which it appears that suppressor cells that inhibit Tc activation or expansion are too dilute to manifest their effect. Moreover, the response was observed in mouse serum-(MS) as well as fetal calf serum- (FCS) supplemented media, an important finding in the light of the anomalous nonspecific effects induced by FCS. The cytotoxic response produced in MS-supplemented media was shown to be highly specific in both the generating and effector phases, whereas the responses in FCS had a strong nonspecific component.

scholarly journals Primary in vitro cell-mediated lympholysis reaction of NZB mice against unmodified targets syngeneic at the major histocompatibility complex.

1978 ◽  
Vol 147 (5) ◽  
pp. 1435-1448 ◽  
Author(s):  
U Botzenhardt ◽  
J Klein ◽  
M Ziff
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
Cell System ◽  
Cytotoxic T Cell ◽  
Mouse Strains ◽  
Major Histocompatibility ◽  
Effector Cells ◽  
Histocompatibility Complex ◽  
2D Strain

T-cell cytotoxicity of NZV mice was tested after in vitro sensitization against a group of H-2 identical strains (BALB/c, B10.D2, DBA/2, HW19). A highly significant and unexpected unidirectional cell-mediated lympholysis (CML) reaction by the sensitized NZB effector cells on these targets was found. After sensitization in vitro with stimulator cells of one H-2d strain, NZB effector cells (H-2d) lysed all other H-2d targets and to a lesser degree, some non-H-2d targets (C57BL/10, DBA/1, B10.Q, CBA, B10.S, A.SW). NZB targets were not lysed. Differences in the major histocompatibility region between NZB and other H-2d strains could be excluded as a possible explanation for the observed reaction of NZB (H-2d) against other H-2d strains. These results consequently represent the first description of a primary in vitro CML directed against determinants not coded for in the major histocompatibility complex. The responsible effector cells are demonstrated to be T cells. The CML of NZB against H-2 identiical targets appears best explained by a reaction against minor histocompatibility antigens. This, and the observed cross-reactions, would indicate that the cytotoxic T-cell system in NZB mice is not subjected to restrictions found in all normal mouse strains tested until now under similar conditions. It is suggested that this hyperreactivity is related to the autoimmune responsiveness of the NZB strain.

scholarly journals Interleukin 10 deficiency attenuates induction of anti-TSH receptor antibodies and hyperthyroidism in a mouse Graves' model

2011 ◽  
Vol 209 (3) ◽  
pp. 353-357 ◽  
Author(s):  
Ikuko Ueki ◽  
Norio Abiru ◽  
Kentaro Kawagoe ◽  
Yuji Nagayama
Keyword(s):  
T Cell ◽  
Cell Function ◽  
Recombinant Adenovirus ◽  
Interleukin 10 ◽  
T Cell Response ◽  
Tsh Receptor ◽  
Mouse Strains ◽  
Susceptible Mouse ◽  
Ifn Γ

Experimental Graves'-like hyperthyroidism can be induced in susceptible mouse strains by repetitive immunizations with recombinant adenovirus expressing the human full-length TSH receptor (TSHR) or its A-subunit. Previous studies have shown that splenocytes from immunized mice produce interferon (IFN)-γ and interleukin (IL) 10 in response to antigen stimulation in an in vitro T cell recall assay. Although IFN-γ is now well known to be essential for disease induction, the role(s) played by IL10 are unknown. Therefore, this study was conducted to clarify the significance of endogenous IL10 in the pathogenesis of experimental Graves' disease using IL10 deficient (IL10−/−) mice. Our results show that T cell response was augmented when estimated by their antigen-specific secretion of the key cytokine IFN-γ, but B cell function was dampened, that is, anti-TSHR antibody titers were decreased in IL10−/− mice, resulting in a lower incidence of Graves' hyperthyroidism (54% in IL10+/+ vs 25% in IL10−/−). Thus, in addition to IFN-γ, these data clarified the role of IL10 for optimizing anti-TSHR antibody induction and eliciting Graves' hyperthyroidism in our Graves' mouse model.

scholarly journals Rapid selection and identification of functional CD8+ T cell epitopes from large peptide-coding libraries

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Govinda Sharma ◽  
Craig M. Rive ◽  
Robert A. Holt
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Epitope ◽  
Cell Receptor ◽  
T Cell Response ◽  
Target Cells ◽  
T Cell Epitopes ◽  
Peptide Epitopes ◽  
Histocompatibility Complex

Abstract Cytotoxic CD8+ T cells recognize and eliminate infected or malignant cells that present peptide epitopes derived from intracellularly processed antigens on their surface. However, comprehensive profiling of specific major histocompatibility complex (MHC)-bound peptide epitopes that are naturally processed and capable of eliciting a functional T cell response has been challenging. Here, we report a method for deep and unbiased T cell epitope profiling, using in vitro co-culture of CD8+ T cells together with target cells transduced with high-complexity, epitope-encoding minigene libraries. Target cells that are subject to cytotoxic attack from T cells in co-culture are isolated prior to apoptosis by fluorescence-activated cell sorting, and characterized by sequencing the encoded minigenes. We then validate this highly parallelized method using known murine T cell receptor/peptide-MHC pairs and diverse minigene-encoded epitope libraries. Our data thus suggest that this epitope profiling method allows unambiguous and sensitive identification of naturally processed and MHC-presented peptide epitopes.

scholarly journals Immunoregulatory circuits that modulate responsiveness to suppressor cell signal. Failure of B10 mice to respond to suppressor factors can be overcome by quenching the contrasuppressor circuit.

1981 ◽  
Vol 153 (6) ◽  
pp. 1547-1561 ◽  
Author(s):  
K Yamauchi ◽  
D R Green ◽  
D D Eardley ◽  
D B Murphy ◽  
R K Gershon
Keyword(s):  
T Cells ◽  
T Cell ◽  
Antibody Response ◽  
Sheep Erythrocyte ◽  
Biologically Active ◽  
Mouse Strains ◽  
Cellular Interactions ◽  
Spleen Cells ◽  
Suppressor Factor

The in vitro antibody response of spleen cells from B10 strain mice is not suppressed by factor preparations made by primed Ly-2 T cells, although these preparations can suppress the in vitro antibody response of spleen cells from other mouse strains (1-3)2. The factor preparations from Ly-2 cells contain at least two separable activities: one that acts as a suppressor moiety (Ly-2 T cell suppressor factor [Ly-2 TsF]) and a second factor that acts as an inducer of contrasuppression (Ly-2 TcsiF); the latter initiates a series of cellular interactions that leads to the inhibition of suppression that we refer to as contrasuppression. Removal of components (either cellular or humoral) of the contrasuppressor circuit makes spleen cells from B10 strain mice as easily suppressible as are those of other mouse strains. Thus, removal of the contrasuppressor inducer cell and/or its biologically active product with the use of an anit-J serum, or removal of the functional acceptor of the inducer cell with the same or other (Ly-2; Qa-1) antisera breaks the B10 suppressor barrier. Contrasuppressive activity. but not helper activity can be eluted from anit-I-J immunoabsorbents. The addition of B10 T cells to either B6 or B10 spleen cell culture deprived of acceptor cells for the TcsiF reconstitutes contrasuppression more efficiently than does the addition of C57BL/6 T cells. Ly-2 TcsiF is more cross-reactive than is Ly-2 TsF so that absorption of factor preparations from sheep erythrocyte-primed Ly-2 cells with horse erythrocytes also breaks the B10 suppressor barrier. The hyperresponsiveness of splenic T cells from B10 strains to Ly-2 TcsiF may be an in vitro exaggeration of a normal in vivo process. Thus it is possible that one can take advantage of this unusual situation to help dissect out the cellular and subcellular components of T cell circuits that moldulate sensitivity to immunoregulatory signals.

scholarly journals Mutual recognition of parental and F1 lymphocytes. Selective abrogation of cytotoxic potential of F1 lymphocytes by parental lymphocytes.

1980 ◽  
Vol 151 (1) ◽  
pp. 20-31 ◽  
Author(s):  
G M Shearer ◽  
R P Polisson
Keyword(s):  
T Cell ◽  
Cytotoxic Activity ◽  
T Lymphocyte ◽  
Mutual Recognition ◽  
Spleen Cells ◽  
Cytotoxic Potential ◽  
F1 Hybrid ◽  
Hybrid Mice ◽  
Lymphocyte Populations

Four different combinations of F1 hybrid mice [(C57BL/10 X B10.A)F1, (C57BL/10 X B10.BR)F1, B6D2F1, and AKD2F1] were injected intravenously with spleen cells from parental strains. The T-cell-mediated cytotoxic potential of spleen cells from the injected F1 mice was assessed from 4 to 21 d later by in vitro sensitization with trinitrophenyl-modified parental or syngeneic F1 spleen cells (TNP-self) or with allogeneic spleen cells. The cytotoxic potential of the F1 mice to TNP-self as well as to alloantigens was abolished or severely depressed throughout this period when the respective H-2k,a,d parental spleen cells were injected. In contrast, the cytotoxic potential was unaffected or only marginally reduced when H-2b parental cells were injected. The induction of depressed cytotoxic activity was shown to be a result of a population of parental radiosensitive T lymphocytes. The results should be discussed with respect to (a) the genetic and mechanistic parameters associated with the differential depressive effects of parental cells expressing H-2b vs. H-2k,a,d antigens, and (b) the use of this system for investigating allogeneic receptors on T-lymphocyte populations.

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