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 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 Cell-mediated lympholysis of trinitrophenyl-modified autologous lymphocytes. Effector cell specificity to modified cell surface components controlled by H-2K and H-2D serological regions of the murine major histocompatibility complex.

1975 ◽  
Vol 141 (6) ◽  
pp. 1348-1364 ◽  
Author(s):  
G M Shearer ◽  
T G Rehn ◽  
C A Garbarino
Keyword(s):  
Major Histocompatibility Complex ◽  
Cell Surface ◽  
Antigenic Determinants ◽  
Mouse Strains ◽  
Target Cells ◽  
Major Histocompatibility ◽  
Resistant Mouse ◽  
Effector Cells ◽  
Histocompatibility Complex

Splenic lymphocytes from four C57BL/10 congenic resistant mouse strains were sensitized in vitro with trinitrophenyl (TNP)-modified autologous spleen cellsmthe effector cells generated were incubated with 51-Cr-labeled unmodified or TNP-modified spleen or tumor target cells, and the percentage of specific lympholysis determined. The results obtained using syngeneic-, congenic-, recombinante, and allogeneic-modified target cells indicated that TNP modification of the target cells was a necessary but insufficient requirement for lympholysis. Intra-H-2 homology either between modified stimulating cells and modified target cells or between responding lymphocytes and modified target cells was also important in the specificity for lysis. Homology at the K serological region or at K plus I-A in the B10.A and B10BR strains, and at either the D serological region or at some other region (possibly K) in the B10.D2 and C57BL/10 strains were shown to be necessary in order to detect lympholysis. Experiments using (B10itimes C57BL/10)F1 responding lymphocytes sensitized and assayed with TNP-modified parental cells indicated that the homology required for lympholysis was between modified stimulating and modified target cellsmthe possibility is raised that histocompatibility antigens may serve in the autologous system as cell surface components which are modified by viruses or autoimmune complexes to form cell-bound modified-self antigens, which are particularly suited for cell-mediated immune reactions. Evidence is presented suggesting that H-2-linked Ir genes are expressed in the TNP-modified autologous cytotoxic system. These findings imply that the major histocompatibility complex can be functionally involved both in the response potential to and in the formation of new antigenic determinants involving modified-self components.

scholarly journals Designer Glycopeptides for Cytotoxic T Cell–based Elimination of Carcinomas

2004 ◽  
Vol 199 (5) ◽  
pp. 707-716 ◽  
Author(s):  
Yanfei Xu ◽  
Sandra J. Gendler ◽  
Alessandra Franco
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
Large Population ◽  
Vaccination Strategy ◽  
Cytotoxic T Cell ◽  
Major Histocompatibility ◽  
Carbohydrate Antigens ◽  
Histocompatibility Complex

Tumors express embryonic carbohydrate antigens called tumor-associated carbohydrate antigens (TACA). TACA-containing glycopeptides are appealing cytotoxic T cell (CTL)-based vaccines to prevent or treat cancer because the same sugar moieties are expressed in a variety of tumors, rendering a vaccination strategy applicable in a large population. Here we demonstrate that by using glycopeptides with high affinity for the major histocompatibility complex and glycosylated in a position corresponding to a critical T cell receptor (TcR) contact, it is possible to induce anti-TACA CTL in vivo. In the current study we show that designer glycopeptides containing the Thomsen-Freidenreich (TF) antigen (β-Gal-[1→3]-α-GalNAc-O-serine) are immunogenic in vivo and generate TF-specific CTL capable of recognizing a variety of tumor cells in vitro including a MUC1-expressing tumor. The fine specificity of the TF-specific CTL repertoire indicates that the TcR recognize the glycosylated amino acid residue together with TF in a conventional major histocompatibility complex class I–restricted fashion. These results have high potential for immunotherapy against a broad range of tumors.

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 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 Use of a lethally irradiated major histocompatibility complex nonrestricted cytotoxic T-cell line for effective purging of marrows containing lysis-sensitive or -resistant leukemic targets [see comments]

Blood ◽  
1996 ◽  
Vol 87 (1) ◽  
pp. 393-403
Author(s):  
A Cesano ◽  
G Pierson ◽  
S Visonneau ◽  
AR Migliaccio ◽  
D Santoli
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
Cell Line ◽  
Autologous Bone Marrow Transplantation ◽  
Leukemia Cell ◽  
Leukemia Cell Line ◽  
Cytotoxic T Cell ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Marrow Purging

Improved marrow purging protocols are needed in autologous bone marrow transplantation (BMT) to achieve complete eradication of minimal residual disease. This study investigates the potential of a human major histocompatibility complex (MHC) nonrestricted killer T-cell line (TALL-104) as a new marrow purging agent in a clinical setting. TALL- 104 cells can be irradiated without losing cytotoxic activity against tumor targets in vitro. In vivo, the irradiated killers can be adoptively transferred into immunodeficient and immunocompetent leukemia-bearing mice, and reverse their disease even in advanced stages. The present study shows that gamma-irradiated TALL-104 cells, cultured for 18 hours with marrows from healthy donors, do not impair the viability and long-term growth of committed and pluripotent hematopoietic progenitors. However, as determined by polymerase chain reaction (PCR) and colony assays, TALL-104 cells could completely purge marrows containing up to 50% lysis-susceptible myelomonocytic leukemia cells (U937). When marrows were admixed with a pre-B leukemia cell line (ALL-1), which is fairly resistant to TALL-104 cell lysis in longterm 51Cr-release assays but can be totally growth inhibited by TALL-104 cells in proliferation assays, residual ALL-1 cells were detectable by PCR after TALL-104 purging. However, importantly, these PCR+ marrows were devoid of tumorigenic activity when transplanted into the human hematopoietic microenvironment of human severe combined immunodeficient (SCID) chimeras. These data indicate the strong potential of the TALL- 104 cell line in future marrow purging strategies against lysis- susceptible and -resistant leukemias.

scholarly journals T cells specific for alpha-beta interface regions of hemoglobin recognize the isolated subunit but not the tetramer and indicate presentation without processing

1989 ◽  
Vol 86 (17) ◽  
pp. 6729-6733 ◽  
Author(s):  
M Z Atassi ◽  
M Yoshioka ◽  
G S Bixler
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
Cell Lines ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Oligomeric Protein ◽  
T Cell Lines ◽  
Antigen Presenting

Processing of a protein antigen into fragments is believed to be a prerequisite for its presentation by the antigen-presenting cell to the T cell. This model would predict that, in oligomeric proteins, T cells prepared with specificity for regions that are buried within subunit association surfaces should recognize the respective regions in vitro equally well on the isolated subunit or on the oligomer. Three hemoglobin (Hb) alpha-chain synthetic peptides, corresponding to areas that are situated either completely [alpha-(31-45)] or partially [alpha-(41-45) and alpha-(81-95)] within the interface between the alpha and beta subunits of Hb, and a fourth peptide representing a completely exposed area in tetrameric Hb were used as immunogens in SJL/J (H-2s) mice. Peptide-primed T cells were passaged in vitro with the respective peptide to obtain peptide-specific T-lymphocyte lines. T-cell clones were isolated from these lines by limiting dilution. T-cell lines and clones that were specific for buried regions in the subunit association surfaces recognized the free peptide and the isolated subunit but not the Hb tetramer. On the other hand, T cells with specificity against regions that are not involved in subunit interaction and are completely exposed in the tetramer recognized the peptide, the isolated subunit, and the oligomeric protein equally well. The responses of the T-cell lines and clones were major histocompatibility complex-restricted. Since the same x-irradiated antigen-presenting cells were employed, the results could not be attributed to differences or defects in Hb processing. The findings indicate that in vitro the native (unprocessed and undissociated) oligomeric protein was the trigger of major histocompatibility complex-restricted T-cell responses.

scholarly journals Use of a lethally irradiated major histocompatibility complex nonrestricted cytotoxic T-cell line for effective purging of marrows containing lysis-sensitive or -resistant leukemic targets [see comments]

Blood ◽  
1996 ◽  
Vol 87 (1) ◽  
pp. 393-403 ◽  
Author(s):  
A Cesano ◽  
G Pierson ◽  
S Visonneau ◽  
AR Migliaccio ◽  
D Santoli
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
Cell Line ◽  
Autologous Bone Marrow Transplantation ◽  
Leukemia Cell ◽  
Leukemia Cell Line ◽  
Cytotoxic T Cell ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Marrow Purging

Abstract Improved marrow purging protocols are needed in autologous bone marrow transplantation (BMT) to achieve complete eradication of minimal residual disease. This study investigates the potential of a human major histocompatibility complex (MHC) nonrestricted killer T-cell line (TALL-104) as a new marrow purging agent in a clinical setting. TALL- 104 cells can be irradiated without losing cytotoxic activity against tumor targets in vitro. In vivo, the irradiated killers can be adoptively transferred into immunodeficient and immunocompetent leukemia-bearing mice, and reverse their disease even in advanced stages. The present study shows that gamma-irradiated TALL-104 cells, cultured for 18 hours with marrows from healthy donors, do not impair the viability and long-term growth of committed and pluripotent hematopoietic progenitors. However, as determined by polymerase chain reaction (PCR) and colony assays, TALL-104 cells could completely purge marrows containing up to 50% lysis-susceptible myelomonocytic leukemia cells (U937). When marrows were admixed with a pre-B leukemia cell line (ALL-1), which is fairly resistant to TALL-104 cell lysis in longterm 51Cr-release assays but can be totally growth inhibited by TALL-104 cells in proliferation assays, residual ALL-1 cells were detectable by PCR after TALL-104 purging. However, importantly, these PCR+ marrows were devoid of tumorigenic activity when transplanted into the human hematopoietic microenvironment of human severe combined immunodeficient (SCID) chimeras. These data indicate the strong potential of the TALL- 104 cell line in future marrow purging strategies against lysis- susceptible and -resistant leukemias.

scholarly journals Role of the major histocompatibility complex in T cell activation of B cell subpopulations. lyb-5(+) and lyb-5(-) B cell subpopulations differ in their requirement for major histocompatibility complex-restricted T cell recognition

1981 ◽  
Vol 154 (2) ◽  
pp. 501-516 ◽  
Author(s):  
A Singer ◽  
PJ Morrissey ◽  
KS Hathcock ◽  
A Ahmed ◽  
I Scher ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cell Recognition ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Cell Subpopulations

This report has examined the requirements for T helper (T(H)) cell recognition of major histocompatibility complex (MHC) determinants expressed by B cells for the activation of unprimed Lyb-5(+) and Lyb-5(-) B cell subpopulations . The generation of primary T(H) cell-dependent plaque-forming cell responses in vitro microculture required the presence of Lyb-5(+) B cells because B cell populations that were deprived, either genetically or serologically, of the Lyb-5(+) subpopulation were not activated in these responses. Cell-mixing experiments in which A X B {arrow} A chimeric T(H) cells were mixed with purified populations of parental accessory cells and parental B cells demonstrated that the in vitro activation of Lyb-5(+) B cells did not require T(H) cell recognition of B cell MHC determinants, although it did require T(H) cell recognition of accessory cell MHC determinants . In contrast to the failure of Lyb-5(-) B cells to be activated in primary T(H) cell-dependent responses in vitro microculture, isolated populations of Lyb-5(-) B cells were triggered by T(H) cells in vivo in short-term adoptive transfer experiments . By the use of A X B {arrow} A chimeric T(H) cells and parental strain B adoptive hosts, it was possible in vivo to distinguish genetically restricted T(H) cell recognition of B cells from genetically restricted T(H) cell recognition of accessory cells. Similar to the results obtained in vitro, the activation in vivo of unfractionated (Lyb-5(+) plus Lyb-5(-)) B cell populations did not require T(H) cell recognition of B cell MHC determinants . In contrast, in the same in vivo responses activation of isolated populations of Lyb-5(-) B cells did require T(H) cell recognition of B cell MHC determinants. The most straightforward interpretation of these experiments is that T(H) cell recognition of B cell MHC determinants is required for the activation of Lyb-5(-) B cells but is not required for the activation of Lyb-5(+) B cells . To better understand why T(H) cell activation of one B cell subpopulation is genetically restricted, whereas activation of another subpopulation is not, the response of Lyb-5(+) and Lyb-5(-) B cells to the soluble activating factors present in concanavalin A-induced spleen cell supernates (Con A SN) was examined. It was observed that Lyb-5(-) B cells, as opposed to Lyb-5(+) B cells, were unable to respond in microculture to the nonspecific T(H) cell- activating factors present in Con A SN, even though they were able to nonspecifically respond under the same conditions to trinitrophenyllipopolysaccharide. It was observed that the ability of B cell subpopulations to respond to nonspecific soluble T cell factors paralleled their ability to be activated by T(H) cells in a genetically unrestricted manner. Thus, the present experiments demonstrate that activation by T(H) cells of Lyb-5(-) B cells is MHC restricted, whereas activation of Lyb-5(+) B cells is not. These experiments suggest that one possible explanation for such differences is that activation of Lyb-5(+) B cells does not require direct interaction with T(H) cells because they can be activated by soluble activation signals that T(H) cells secrete.

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