scholarly journals Xenogeneic human anti-mouse T cell responses are due to the activity of the same functional T cell subsets responsible for allospecific and major histocompatibility complex-restricted responses.

1983 ◽  
Vol 157 (2) ◽  
pp. 720-729 ◽  
Author(s):  
S L Swain ◽  
R W Dutton ◽  
R Schwab ◽  
J Yamamoto
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
T Cell Subsets ◽  
Class I ◽  
Major Histocompatibility ◽  
Class I Mhc ◽  
Mhc Antigens ◽  
Histocompatibility Complex ◽  
Mouse Class

Human T cells respond strongly to mouse major histocompatibility complex (MHC) antigens. The response is directed predominantly to the polymorphic determinants of the MHC antigens and there is little or no response to the nonpolymorphic determinants or to non-MHC antigens. Human cytotoxic T lymphocytes (CTL) are generated specific for the mouse class I MHC antigens and the CTL effectors are blocked by anti-Leu-2a antisera. Human interleukin 2-producing T cells are generated specific for mouse class II antigens and their induction is blocked by anti-Leu-3a antisera. These and other considerations lead us to propose a model for the T cell receptor that provides an explanation for several of the features of T cell recognition. In this model, the recognition of the "class" (I or II) of MHC antigen is separate from the recognition of the polymorphic determinants. We suggest that the initial recognition of the conserved "class" determinants positions another domain of the receptor so that it can only engage with the part of the MHC molecule carrying the polymorphic determinants.

scholarly journals Greatly reduced lymphoproliferation in lpr mice lacking major histocompatibility complex class I.

1995 ◽  
Vol 181 (2) ◽  
pp. 641-648 ◽  
Author(s):  
M A Maldonado ◽  
R A Eisenberg ◽  
E Roper ◽  
P L Cohen ◽  
B L Kotzin
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
Class Ii ◽  
T Cell Subsets ◽  
Cell Surface Receptor ◽  
Class I ◽  
Major Histocompatibility ◽  
Gamma Delta ◽  
Histocompatibility Complex

Mice homozygous for the lpr gene have a defect in fas (CD95), a cell surface receptor that belongs to the tumor necrosis factor receptor family and that mediates apoptosis. This genetic abnormality results in lymphoproliferation characterized by the accumulation of CD4-CD8- (double negative [DN]) T cells, autoantibody production, and background strain-dependent, end-organ disease. Our previous results suggested that major histocompatibility complex (MHC) class I may be involved in the development of DN cells. To test this hypothesis, we derived C57BL/6-lpr/lpr (B6/lpr) mice that were deficient for the beta 2-microglobulin gene (beta 2m lpr) and had no detectable class I expression. At 6 mo of age, compared with B6/lpr littermates with normal class I genes, these mice showed greatly reduced lymphadenopathy, mostly due to a dramatic decrease in the number of DN cells. Significant changes in the percentage of other T cell subsets were noted, but only gamma/delta+ T cells showed a marked increase in both percentage and absolute numbers. Analysis of T cell receptor V beta expression of the remaining DN T cells in beta 2m -lpr mice showed a shift to a CD4-like repertoire from a CD8-like repertoire in control B6/lpr mice, indicating that a small MHC class II selected DN population was unmasked in lpr mice lacking class I. We also found that the production of immunoglobulin G (IgG) autoantibodies (antichromatin and anti-single stranded DNA), total IgG and IgG2a, but not total IgM or IgM rheumatoid factor, was significantly reduced in the beta 2m -lpr mice. This work suggests that >90% of DN T cells in lpr mice are derived from the CD8 lineage and are selected on class I. However, a T cell subset selected on class II and T cells expressing gamma/delta are also affected by the lpr defect and become minor components of the aberrant DN population.

scholarly journals Clone-specific T cell receptor antagonists of major histocompatibility complex class I-restricted cytotoxic T cells.

1993 ◽  
Vol 177 (6) ◽  
pp. 1541-1550 ◽  
Author(s):  
S C Jameson ◽  
F R Carbone ◽  
M J Bevan
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Class I ◽  
Major Histocompatibility ◽  
Class I Mhc ◽  
Histocompatibility Complex ◽  
T Cell Clone

A previous report showed that the proliferative response of helper T cells to class II major histocompatibility complex (MHC)-restricted antigens can be inhibited by analogues of the antigen, which act as T cell receptor (TCR) antagonists. Here we define and analyze peptide variants that antagonize various functions of class I MHC-restricted cytotoxic T lymphocyte (CTL) clones. Of 64 variants at individual TCR contact sites of the Kb-restricted octamer peptide ovalbumin257-264 (OVAp), a very high proportion (40%) antagonized lysis by three OVAp-specific CTL clones. This effect was highly clone specific, since many antagonists for one T cell clone have differential effects on another. We show that this inhibition of CTL function is not a result of T cell-T cell interaction, precluding veto-like phenomena as a mechanism for antagonism. Moreover, we present evidence for direct interaction between the TCR and antagonist-MHC complexes. In further analysis of the T cell response, we found that serine esterase release and cytokine production are susceptible to TCR antagonism similarly to lysis. Ca2+ flux, an early event in signaling, is also inhibited by antagonists but may be more resistant to the antagonist effect than downstream responses.

scholarly journals Activation of Stat-3 Is Involved in the Induction of Apoptosis After Ligation of Major Histocompatibility Complex Class I Molecules on Human Jurkat T Cells

Blood ◽  
1998 ◽  
Vol 91 (10) ◽  
pp. 3566-3573 ◽  
Author(s):  
Søren Skov ◽  
Mette Nielsen ◽  
Søren Bregenholt ◽  
Niels Ødum ◽  
Mogens H. Claesson
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
Major Histocompatibility Complex Class ◽  
Class I ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Jurkat T Cells ◽  
Class I Mhc ◽  
Mhc I ◽  
Histocompatibility Complex

Abstract Activation of Janus tyrosine kinases (Jak) and Signal transducers and activators of transcription (Stat) after ligation of major histocompatibility complex class I (MHC-I) was explored in Jurkat T cells. Cross-linking of MHC-I mediated tyrosine phosphorylation of Tyk2, but not Jak1, Jak2, and Jak3. In addition, the transcription factor Stat-3 was tyrosine phosphorylated in the cytoplasma and subsequently translocated to the cell nucleus. Data obtained by electrophoretic mobility shift assay suggested that the activated Stat-3 protein associates with the human serum-inducible element (hSIE) DNA-probe derived from the interferon-γ activated site (GAS) in the c-fos promoter, a common DNA sequence for Stat protein binding. An association between hSIE and Stat-3 after MHC-I ligation was directly demonstrated by precipitating Stat-3 from nuclear extracts with biotinylated hSIE probe and avidin-coupled agarose. To investigate the function of the activated Stat-3, Jurkat T cells were transiently transfected with a Stat-3 isoform lacking the transactivating domain. This dominant-negative acting Stat-3 isoform significantly inhibited apoptosis induced by ligation of MHC-I. In conclusion, our data suggest the involvement of the Jak/Stat signal pathway in MHC-I–induced signal transduction in T cells.

scholarly journals Immunogenicity and tolerogenicity of self-major histocompatibility complex peptides.

1990 ◽  
Vol 172 (5) ◽  
pp. 1341-1346 ◽  
Author(s):  
G Benichou ◽  
P A Takizawa ◽  
P T Ho ◽  
C C Killion ◽  
C A Olson ◽  
...  
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
Class Ii ◽  
Class I ◽  
Major Histocompatibility ◽  
Autoreactive T Cells ◽  
Mhc Molecules ◽  
Histocompatibility Complex ◽  
Self Tolerance

Mechanisms involved in self-antigen processing and presentation are crucial in understanding the induction of self-tolerance in the thymus. We examined the immunogenicity of determinants from major histocompatibility complex (MHC) molecules that are expressed in the thymus and have tested peptides derived from the polymorphic regions of class I and class II molecules. We found that two peptides corresponding to NH2 termini of the class II alpha and beta chains (Ak alpha 1-18 and Ak beta 1-16) could bind to self-Ak molecules with high affinity and, surprisingly, were immunogenic in that they could elicit strong proliferative T cell responses in B10.A mice (Ak, Ek). Neonatal injection of peptide Ak beta 1-16 resulted in complete unresponsiveness to this peptide at 8 wk of age showing that these T cells were susceptible to tolerance induction. We have also tested certain class I MHC peptides and showed that some can interact efficiently with class II MHC peptides to induce an autoreactive T cell proliferative response. Among these class I peptides is one (Dd 61-85) that has the capacity to bind to self-Ia without being immunogenic, and therefore represents an MHC determinant that had induced thymic self-tolerance. We conclude that some self-MHC molecules can be processed into peptides that can be presented in the context of intact class II molecules at the surface of antigen-presenting cells. Autoreactive T cells recognizing optimally processed self-peptide/MHC complexes are eliminated during development, whereas other potentially autoreactive T cells escape clonal inactivation or deletion. Incomplete tolerance to self-antigens enriches the T cell repertoire despite the fact that such T cells may eventually become involved in autoimmune disease.

Myofiber Expression of Class I Major Histocompatibility Complex Accompanied by CD8+ T-cell-associated Myofiber Injury in a Case of Canine Polymyositis

2002 ◽  
Vol 39 (4) ◽  
pp. 512-515 ◽  
Author(s):  
T. Morita ◽  
A. Shimada ◽  
S. Yashiro ◽  
T. Takeuchi ◽  
Y. Hikasa ◽  
...  
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
Mhc Class I ◽  
Plasma Cells ◽  
Early Stage ◽  
Cd8 T Cell ◽  
Class I ◽  
Major Histocompatibility ◽  
Histocompatibility Complex

A 7-year-old female Labrador Retriever dog showed extreme muscular weakness, muscle wasting, dysbasia, and mild dysphagia. An elevated value of creatine kinase (335 IU/liter) in the serum was detected. Electromyographic findings included increased insertional activity, fibrillation potentials, and bizarre high-frequency repetitive potentials. Histopathologic examination of skeletal muscles revealed myofiber necrosis and phagocytosis, regeneration of myofibers, and perivascular, perimysial, and endomysial infiltrations of lymphocytes, macrophages and plasma cells. Immunohistochemical evaluation demonstrated that infiltrative cells in the early stage of myositis were CD8+ T-cells and that an increased expression of major histocompatibility complex (MHC) class I was apparent on the surface of nonnecrotic muscle fibers. In contrast, many CD3+ cells (T cells) and HLA-DR-positive macrophages and B lymphocytes were found in the severely affected areas. These results suggest that both expression of MHC class I and CD8+ T-cell infiltration may play an important role in initiation of myositis. These histopathologic findings resemble those reported in naturally occurring polymyositis in humans.

scholarly journals Making the Most of Major Histocompatibility Complex Molecule Multimers: Applications in Type 1 Diabetes

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Greg S. Gojanovich ◽  
Paul R. Hess
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
T Lymphocytes ◽  
T Cell Subsets ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Pancreatic Islets Of Langerhans

Classical major histocompatibility complex (MHC) class I and II molecules present peptides to cognate T-cell receptors on the surface of T lymphocytes. The specificity with which T cells recognize peptide-MHC (pMHC) complexes has allowed for the utilization of recombinant, multimeric pMHC ligands for the study of minute antigen-specific T-cell populations. In type 1 diabetes (T1D), CD8+ cytotoxic T lymphocytes, in conjunction with CD4+ T helper cells, destroy the insulin-producingβcells within the pancreatic islets of Langerhans. Due to the importance of T cells in the progression of T1D, the ability to monitor and therapeutically target diabetogenic clonotypes of T cells provides a critical tool that could result in the amelioration of the disease. By administering pMHC multimers coupled to fluorophores, nanoparticles, or toxic moieties, researchers have demonstrated the ability to enumerate, track, and delete diabetogenic T-cell clonotypes that are, at least in part, responsible for insulitis; some studies even delay or prevent diabetes onset in the murine model of T1D. This paper will provide a brief overview of pMHC multimer usage in defining the role T-cell subsets play in T1D etiology and the therapeutic potential of pMHC for antigen-specific identification and modulation of diabetogenic T cells.

scholarly journals Thymic selection of CD8+ single positive cells with a class II major histocompatibility complex-restricted receptor.

1994 ◽  
Vol 180 (1) ◽  
pp. 25-34 ◽  
Author(s):  
J Kirberg ◽  
A Baron ◽  
S Jakob ◽  
A Rolink ◽  
K Karjalainen ◽  
...  
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
Cell Receptor ◽  
Class Ii ◽  
Major Histocompatibility ◽  
Class I Mhc ◽  
Mhc Molecules ◽  
Histocompatibility Complex ◽  
Alpha Beta

We describe mice that express a transgenic T cell receptor alpha/beta (TCR-alpha/beta) specific for peptide 111-119 from influenza hemagglutinin presented by I-Ed class II major histocompatibility complex (MHC) molecules. The transgenic TCR is expressed on CD4+8- as well as CD4-8+ mature T cells even in mice that are deficient in rearrangement or do not express endogenous TCR-alpha genes. The CD4-8+ T cells require I-Ed class II MHC molecules for positive selection and can be activated to proliferate and to kill by I-Ed molecules presenting the relevant peptide. Full maturation of these cells, however, also requires the presence of class I MHC molecules. The results are compatible with the notion that T cell maturation requires multiple receptor-ligand interactions and establish an exception to the rule that class II-restricted TCRs are exclusively expressed by mature CD4+8- cells.

scholarly journals Homologies between cell interaction molecular controlled by major histocompatibility complex- and Igh-V-linked genes that T cells use for communication. Tandem "adaptive" differentiation of producer and acceptor cells.

1982 ◽  
Vol 156 (5) ◽  
pp. 1390-1397 ◽  
Author(s):  
P Flood ◽  
K Yamauchi ◽  
A Singer ◽  
R K Gershon
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
Variable Region ◽  
Cell Interaction ◽  
T Cell Subsets ◽  
Genetic Constitution ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Communication Events

We have asked the question: how do partner cells in immunoregulatory interactions between T cell subsets acquire the ability to recognize and react appropriately with one another? In particular, we have asked whether these communication events are completely determined by the cell's genetic constitution, or whether the recognition events can be learned during ontogeny. We have found that the T cells of parent into F1 chimeras and homozygous nude mice with F1 thymus grafts not only learn to react with genetically disparate acceptor cells, but that the receptors on the acceptor cells themselves learn to react with genetically disparate producer cells. This learning process can overcome both major histocompatibility complex- and immunoglobulin heavy chain variable region-linked restricted communication between T cell subsets. We interpret these findings to indicate that thymic elements can start a cascade of differential events. The thymic elements, whether endogenous or passively acquired, select from a pool of producer cells those that will react appropriately with the thymic selecting cells, and these cells become expanded. Then, the private markers (idiotype) on the expanded pool of producer cells act as selecting and expanding elements that choose from a pool of acceptor cells those that recognize the producer cells idiotype as self. This second differentiational event, although apparently thymus evidence that this type of acceptor cell differentiation could also take place during the course of an immune response.

scholarly journals Activation of Stat-3 Is Involved in the Induction of Apoptosis After Ligation of Major Histocompatibility Complex Class I Molecules on Human Jurkat T Cells

Blood ◽  
1998 ◽  
Vol 91 (10) ◽  
pp. 3566-3573
Author(s):  
Søren Skov ◽  
Mette Nielsen ◽  
Søren Bregenholt ◽  
Niels Ødum ◽  
Mogens H. Claesson
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
Major Histocompatibility Complex Class ◽  
Class I ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Jurkat T Cells ◽  
Class I Mhc ◽  
Mhc I ◽  
Histocompatibility Complex

Activation of Janus tyrosine kinases (Jak) and Signal transducers and activators of transcription (Stat) after ligation of major histocompatibility complex class I (MHC-I) was explored in Jurkat T cells. Cross-linking of MHC-I mediated tyrosine phosphorylation of Tyk2, but not Jak1, Jak2, and Jak3. In addition, the transcription factor Stat-3 was tyrosine phosphorylated in the cytoplasma and subsequently translocated to the cell nucleus. Data obtained by electrophoretic mobility shift assay suggested that the activated Stat-3 protein associates with the human serum-inducible element (hSIE) DNA-probe derived from the interferon-γ activated site (GAS) in the c-fos promoter, a common DNA sequence for Stat protein binding. An association between hSIE and Stat-3 after MHC-I ligation was directly demonstrated by precipitating Stat-3 from nuclear extracts with biotinylated hSIE probe and avidin-coupled agarose. To investigate the function of the activated Stat-3, Jurkat T cells were transiently transfected with a Stat-3 isoform lacking the transactivating domain. This dominant-negative acting Stat-3 isoform significantly inhibited apoptosis induced by ligation of MHC-I. In conclusion, our data suggest the involvement of the Jak/Stat signal pathway in MHC-I–induced signal transduction in T cells.

scholarly journals Constitutive CD8 expression allows inefficient maturation of CD4+ helper T cells in class II major histocompatibility complex mutant mice.

1994 ◽  
Vol 179 (6) ◽  
pp. 1997-2004 ◽  
Author(s):  
E Robey ◽  
A Itano ◽  
W C Fanslow ◽  
B J Fowlkes
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
Cd4 T Cells ◽  
Class Ii ◽  
Class I ◽  
Major Histocompatibility ◽  
Cd4 Cells ◽  
Class I Mhc ◽  
Histocompatibility Complex ◽  
Class Ii Mhc

Although mature CD4+ T cells bear T cell receptors (TCRs) that recognize class II major histocompatibility complex (MHC) and mature CD8+ T cells bear TCRs that recognize class I MHC, it is possible that the initial commitment of an immature thymocyte to a CD4 or CD8 lineage is made without regard to the specificity of the TCR. According to this model, CD4+ cells with class I TCR do not mature because the CD8 coreceptor is required for class I MHC recognition and positive selection. If this model is correct, constitutive expression of CD8 should allow CD4+ T cells with class I-specific TCRs to develop. In this report, we show that mature peripheral CD4+ cells are present in class II MHC-deficient mice that express a constitutive CD8.1 transgene. These cells share a number of properties with the major class II MHC-selected CD4 population, including the ability to express CD40 ligand upon activation. Although mature CD4 cells are also detectable in the thymus of class II MHC mutant/CD8.1 transgenic mice, they represent a small fraction of the mature CD4 cells found in mice that express class II MHC. These results indicate that some T cells choose the CD4 helper lineage independent of their antigen receptor specificity; however, the inefficiency of generating class I-specific CD4 cells leaves open the possibility that an instructive signal generated upon MHC recognition may bias lineage commitment.

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