scholarly journals Major histocompatibility complex-specific prolongation of murine skin and cardiac allograft survival after in vivo depletion of V beta+ T cells.

1993 ◽  
Vol 177 (1) ◽  
pp. 35-44 ◽  
Author(s):  
J A Goss ◽  
R Pyo ◽  
M W Flye ◽  
J M Connolly ◽  
T H Hansen
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
Intraperitoneal Administration ◽  
Cell Receptor ◽  
Primary Response ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Allogeneic Response

The preferential usage of certain T cell receptor (TCR) V beta genes has been well established in several major histocompatibility complex (MHC)-restricted immune responses. However, V beta usage among allogeneic responses remains unclear. Because recent findings of ours and others indicate that V beta 8 predominates in certain Ld-restricted, peptide-specific responses, we examined the V beta 8 usage in allogeneic responses to Ld. To selectively recognize the Ld molecule, cells from BALB/c-H-2dm2 (dm2), the Ld-loss mutant mouse, were stimulated in vitro or in vivo with wild-type BALB/c cells. We report here that after the intraperitoneal administration of the anti-V beta 8 monoclonal antibody (mAb) F23.1, peripheral V beta 8 T cells were depleted from dm2 mice. This in vivo depletion abrogated the ability of dm2 splenocytes to mount a primary response to Ld molecules. This abrogation was specific, since the response of V beta 8-depleted dm2 cells to Kb/Db antigens was the same as that of control nondepleted dm2 cells. Furthermore, in vivo depletion of V beta 8 cells was found to cause a dramatic prolongation of Ld-disparate skin grafts (mean survival time [MST] 22.1 +/- 2.1 vs. 10.3 +/- 1.1 d for saline-treated controls, or 10.9 +/- 1.7 d for controls treated with mAb KJ23 to V beta 17). By contrast, V beta 8 depletion had no effect on recipients grafted with haplotype-mismatched skin or single Dk-locus-disparate skin. These findings demonstrate that V beta 8+ T cells predominate in allogeneic response to Ld but not other alloantigens. The effect of V beta 8 depletion was found to be even more dramatic on recipients grafted with Ld-disparate vascularized heart transplants (MST > 100 vs. 8.6 +/- 0.5 d for controls). In total, these findings establish the efficacy of using mAb to the V beta gene family to specifically and significantly enhance the survival of allografts. The implications of detecting V beta 8 usage in both alloreactive or MHC-restricted TCR responses to the same class I molecule are discussed.

scholarly journals Disease inhibition by major histocompatibility complex binding peptide analogues of disease-associated epitopes: more than blocking alone.

1992 ◽  
Vol 176 (3) ◽  
pp. 667-677 ◽  
Author(s):  
M H Wauben ◽  
C J Boog ◽  
R van der Zee ◽  
I Joosten ◽  
A Schlief ◽  
...  
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
Major Histocompatibility ◽  
In Vitro Proliferation ◽  
Histocompatibility Complex ◽  
Disease Induction ◽  
Immunomodulatory Peptides ◽  
Peptide Analogues

Peptide analogues of disease-associated epitopes were studied for inhibition of experimental allergic encephalomyelitis (EAE) and adjuvant arthritis (AA) in Lewis rats. EAE- and AA-associated analogues were selected as competitors because of their in vitro inhibitory activity on proliferation of encephalitogenic and arthritogenic T cells. Although the EAE-associated competitor had a superior major histocompatibility complex (MHC) binding affinity, the AA-associated competitor was a better inhibitor of the in vitro proliferation of arthritogenic T cells. Furthermore, although in vivo EAE was inhibited by both competitors, AA was only inhibited by the AA-associated competitor. Remarkably, in contrast to what was expected of a regular MHC competitor peptide, the AA-associated peptide analogue also prevented AA upon immunization before disease induction and appeared to induce T cell responses that crossreacted with the original disease-associated epitope. Therefore, it is concluded that antigen-specific regulatory mechanisms were involved in synergy with MHC competition. The integration of both qualities into a single "competitor-modulator" analogue peptide may lead to the development of novel, more effective, disease-specific immunomodulatory peptides.

scholarly journals The major histocompatibility complex-restricted antigen receptor on T cells. II. Role of the L3T4 product.

1983 ◽  
Vol 158 (4) ◽  
pp. 1077-1091 ◽  
Author(s):  
P Marrack ◽  
R Endres ◽  
R Shimonkevitz ◽  
A Zlotnik ◽  
D Dialynas ◽  
...  
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
Cell Receptor ◽  
Surface Expression ◽  
High Avidity ◽  
Low Doses ◽  
Major Histocompatibility ◽  
Histocompatibility Complex

We have examined the role of the murine homologue of Leu-3 T4, L3T4, in recognition of antigen in association with products of the major histocompatibility complex (Ag/MHC) by murine T cell hybridomas. A series of ovalbumin (OVA)/I-Ad-specific T cell hybridomas were ranked in their sensitivity to Ag/I by measuring their ability to respond to low doses of OVA, or their sensitivity to inhibition by anti-I-Ad antibodies. T cell hybridomas with low apparent avidity for OVA/I-Ad, i.e. that did not respond well to low concentrations of OVA and were easily inhibited by anti-I-Ad, were also easily inhibited by anti-L3T4 antibodies. The reverse was true for T cell hybridomas with apparent high avidity for Ag/MHC. We found that the presence of low doses of anti-L3T4 antibodies caused T cell hybridomas to respond less well to low doses of Ag, and to be more easily inhibited by anti-I-Ad antibodies. These results suggested that the role of the L3T4 molecule is to increase the overall avidity of the reaction between T cells and Ag-presenting cells. In support of this idea was the discovery of several L3T4- subclones of one of our L3T4+ T cell hybridomas, D0.11.10. The L3T4- subclones had the same amount of receptor for OVA/I-Ad as their L3T4+ parent, as detected by an anti-receptor monoclonal antibody. The L3T4- subclones, however, responded less well to low doses of OVA, and were more easily inhibited by anti-I-Ad antibodies than their L3T4/ parent. These results showed that the L3T4 molecule was not required for surface expression of, or functional activity of, the T cell receptor for Ag/MHC. The L3T4 molecule did, however, increase the sensitivity with which the T cell reacted with Ag/MHC on Ag-presenting cells.

Abstract 124: Parthenogenetic Stem Cell-derived Cardiomyocytes Express Major Histocompatibility Complex-I only after Inflammatory Stimulation

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Satish Galla ◽  
Michael Didie ◽  
Vijayakumar Muppala ◽  
Ralf Dressel ◽  
Wolfram Hubertus Zimmermann
Keyword(s):  
Major Histocompatibility Complex ◽  
Heart Muscle ◽  
Immunological Response ◽  
Type I ◽  
Major Histocompatibility ◽  
Adrenergic Stimulation ◽  
Mhc I ◽  
Histocompatibility Complex

Background: Pluripotent parthenogenetic stem cells (PSCs) can be directed towards a cardiac fate and utilized in tissue engineered heart repair. In vivo applications of tissue engineered allografts are compromised by expression of mismatching major histocompatibility complex proteins (MHC; encoded in the murine H2 locus). Here we investigated whether PSC-derived cardiomyocytes (CM) express MHC-I. Methods: Mouse PSCs (A3-line from B6D2F1 strain with haploidentical H2K d -locus) expressing a CM-specific neomycin-resistance and GFP were differentiated and purified for CM by addition of G418 (85% purity by FACS for actinin). To simulate heart muscle biology in vitro, we made use of engineered heart muscle (EHM) constructed from PSC-derived CM (75%), growth-inhibited murine embryonic fibroblasts (MEF (25%); NMRI mice), and collagen type I. MHC class-I H2K d (MHC-I) expression was assessed on CM and Non myocytes before EHM assembly and from enzymatically digested EHMs (cultured for 10 days) by FACS. Interferon gamma (IFNγ) was added for 48 h to stimulate MHC-I expression. As a reference, we investigated MHC-I expression in CM from neonatal mice and adult mouse hearts by FACS and by immunofluorescence staining. Results: EHM showed a positive ionotropic response to beta-adrenergic stimulation which could be reduced by muscarinergic stimulation. A3-CM, in contrast to Non myocytes, showed negligible expression of MHC-I (1±0.5% vs. 60±10% positive cells; n=3). EHM culture did not change MHC-I expression in CM. IFNγ treatment resulted in a marked increase of MHC-I-expression in CM monolayer culture (40±6%; n=3) and in EHM (30±8%; n=3). For comparison, 30% (n=2) neonatal CM expressed MHC-I while MHC-I was not detectable in adult CM. Conclusion: PSC-derived CM show a similarly low expression of MHC-I as adult CM and respond with MHC-I upregulation to IFNγ stimulation. This suggests a mature immunological response in PSC-CM with important implications for in vivo applications, i.e., MHC-I matching will likely be a prerequisite for successful allografting of PSC-EHM.

scholarly journals Hematopoietic lineage-converted T cells carrying tumor-associated antigen-recognizing TCRs effectively kill tumor cells

2020 ◽  
Vol 8 (2) ◽  
pp. e000498
Author(s):  
Fangxiao Hu ◽  
Dehao Huang ◽  
Yuxuan Luo ◽  
Peiqing Zhou ◽  
Cui Lv ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Tumor Cells ◽  
Cell Receptor ◽  
Histocompatibility Complex ◽  
Tumor Associated Antigen ◽  
Engineered T Cells ◽  
Antitumor Immunotherapy

Tumor-associated antigen (TAA) T-cell receptor (TCR) gene-engineered T cells exhibit great potential in antitumor immunotherapy. Considering the high costs and low availability of patient-derived peripheral blood T cells, substantial efforts have been made to explore alternatives to natural T cells. We previously reported that enforced expression of Hoxb5 converted B cells into induced T (iT) cells in vivo. Here, we successfully regenerated naive OT1 (major histocompatibility complex I restricted ovalbumin antigen) iT cells (OT1-iT) in vivo by expressing Hoxb5 in pro-pre-B cells in the OT1 transgenic mouse. The OT1-iT cells can be activated and expanded in vitro in the presence of tumor cells. Particularly, these regenerated OT1-iT cells effectively eradicated tumor cells expressing the TAA (ovalbumin) both in vitro and in vivo. This study provides insights into the translational applications of blood lineage-transdifferentiated T cells in immunotherapy.

scholarly journals Major Histocompatibility Complex Haplotype Determines hsp70-Dependent Protection against Measles Virus Neurovirulence

2009 ◽  
Vol 83 (11) ◽  
pp. 5544-5555 ◽  
Author(s):  
Thomas Carsillo ◽  
Mary Carsillo ◽  
Zachary Traylor ◽  
Päivi Rajala-Schultz ◽  
Phillip Popovich ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Measles Virus ◽  
Protective Role ◽  
Major Histocompatibility ◽  
Major Histocompatibility Complex Haplotype ◽  
Brain Infection ◽  
Histocompatibility Complex ◽  
The Impact

ABSTRACT In vitro studies show that hsp70 promotes gene expression for multiple viral families, although there are few reports on the in vivo significance of virus-hsp70 interaction. Previously we showed that hsp70-dependent stimulation of Edmonston measles virus (Ed MeV) transcription caused an increased cytopathic effect and mortality in transgenic hsp70-overexpressing C57BL/6 mice (H-2 b ). The response to MeV infection is influenced by the major histocompatibility complex haplotype; H-2 d mice are resistant to brain infection due to robust antiviral immune responses, whereas H-2 b mice are susceptible due to deficiencies in this response. We therefore tested the hypothesis that the outcome of MeV-hsp70 interaction may be dependent upon the host H-2 haplotype. The impact of selective neuronal hsp70 overexpression on Ed MeV brain infection was tested with congenic C57BL/10 H-2 d neonatal mice. In this context, hsp70 overexpression conferred complete protection against virus-induced mortality, compared to >30% mortality in nontransgenic mice. Selective depletion of T-cell populations showed that transgenic mice exhibit a diminished reliance on T cells for protection. Brain transcript analysis indicated enhanced innate immune activation and signaling through Toll-like receptors 2 and 4 at early times postinfection for transgenic infected mice relative to those for nontransgenic infected mice. Collectively, results suggest that hsp70 can enhance innate antiviral immunity through Toll-like receptor signaling, supporting a protective role for physiological responses that enhance tissue levels of hsp70 (e.g., fever), and that the H-2 haplotype determines the effectiveness of this response.

scholarly journals Peripheral Blood Mucosal-Associated Invariant T Cells in Tuberculosis Patients and Healthy Mycobacterium tuberculosis-Exposed Controls

2020 ◽  
Vol 222 (6) ◽  
pp. 995-1007 ◽  
Author(s):  
Sara Suliman ◽  
Anele Gela ◽  
Simon C Mendelsohn ◽  
Sarah K Iwany ◽  
Kattya Lopez Tamara ◽  
...  
Keyword(s):  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
Major Histocompatibility Complex ◽  
Cell Receptor ◽  
Surface Markers ◽  
Strongly Correlated ◽  
Major Histocompatibility ◽  
Mait Cells ◽  
Histocompatibility Complex ◽  
Variable Gene

Abstract Background In human blood, mucosal-associated invariant T (MAIT) cells are abundant T cells that recognize antigens presented on non-polymorphic major histocompatibility complex-related 1 (MR1) molecules. The MAIT cells are activated by mycobacteria, and prior human studies indicate that blood frequencies of MAIT cells, defined by cell surface markers, decline during tuberculosis (TB) disease, consistent with redistribution to the lungs. Methods We tested whether frequencies of blood MAIT cells were altered in patients with TB disease relative to healthy Mycobacterium tuberculosis-exposed controls from Peru and South Africa. We quantified their frequencies using MR1 tetramers loaded with 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil. Results Unlike findings from prior studies, frequencies of blood MAIT cells were similar among patients with TB disease and latent and uninfected controls. In both cohorts, frequencies of MAIT cells defined by MR1-tetramer staining and coexpression of CD161 and the T-cell receptor alpha variable gene TRAV1-2 were strongly correlated. Disease severity captured by body mass index or TB disease transcriptional signatures did not correlate with MAIT cell frequencies in patients with TB. Conclusions Major histocompatibility complex (MHC)-related 1-restrictied MAIT cells are detected at similar levels with tetramers or surface markers. Unlike MHC-restricted T cells, blood frequencies of MAIT cells are poor correlates of TB disease but may play a role in pathophysiology.

scholarly journals Donor major histocompatibility complex (MHC) peptides are presented by recipient MHC molecules during graft rejection.

1992 ◽  
Vol 175 (1) ◽  
pp. 305-308 ◽  
Author(s):  
G Benichou ◽  
P A Takizawa ◽  
C A Olson ◽  
M McMillan ◽  
E E Sercarz
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
Critical Role ◽  
Major Histocompatibility ◽  
Skin Allograft ◽  
Mhc Molecules ◽  
Histocompatibility Complex ◽  
Molecular Therapies ◽  
Antigen Presenting

Peptides from donor major histocompatibility complex (MHC) molecules were examined for their activation of allogeneically primed T cells. After immunization with either allogeneic spleen cells or a skin allograft, primed T cells proliferate in response to peptides derived from polymorphic regions of alpha and beta chains of class II allo-MHC molecules. The results demonstrate that presentation of donor-MHC peptides by host-derived antigen-presenting cells is a common event in vivo. Thus, self-restricted T cell recognition of processed alloantigens may play a critical role in transplantation. An in-depth understanding of this response may result in the development of additional molecular therapies to combat allograft rejection.

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