scholarly journals Major Histocompatibility Complex Class II–Positive Cortical Epithelium Mediates the Selection of Cd4+25+ Immunoregulatory T Cells

2001 ◽  
Vol 194 (4) ◽  
pp. 427-438 ◽  
Author(s):  
Steven J. Bensinger ◽  
Antonio Bandeira ◽  
Martha S. Jordan ◽  
Andrew J. Caton ◽  
Terri M. Laufer
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
Mhc Class Ii ◽  
Antigen Presenting Cells ◽  
Class Ii ◽  
Histocompatibility Complex ◽  
Antigen Presenting ◽  
Immunoregulatory T Cells ◽  
Deficient Mice ◽  
Selection Of

CD4+25+ T cells are a unique population of immunoregulatory T cells which are critical for the prevention of autoimmunity. To address the thymic selection of these cells we have used two models of attenuated thymic deletion. In K14-Aβb mice, major histocompatibility complex (MHC) class II I-Ab expression is limited to thymic cortical epithelium and deletion by hematopoietic antigen-presenting cells does not occur. In H2-DMα–deficient mice, MHC class II molecules contain a limited array of self-peptides resulting in inefficient clonal deletion. We find that CD4+25+ T cells are present in the thymus and periphery of K14-Aβb and H2-DMα–deficient mice and, like their wild-type counterparts, suppress the proliferation of cocultured CD4+25− effector T cells. In contrast, CD4+25+ T cells from MHC class II–deficient mice do not suppress responder CD4+ T cells in vitro or in vivo. Thus, development of regulatory CD4+25+ T cells is dependent on MHC class II-positive thymic cortical epithelium. Furthermore, analysis of the specificities of CD4+25+ T cells in K14-Aβb and H2-DMα–deficient mice suggests that a subset of CD4+25+ T cells is subject to negative selection on hematopoietic antigen-presenting cells.

scholarly journals A novel antigen-processing-defective phenotype in major histocompatibility complex class II-positive CIITA transfectants is corrected by interferon-gamma.

1995 ◽  
Vol 182 (6) ◽  
pp. 1793-1799 ◽  
Author(s):  
C A Siegrist ◽  
E Martinez-Soria ◽  
I Kern ◽  
B Mach
Keyword(s):  
Major Histocompatibility Complex ◽  
Mhc Class Ii ◽  
Interferon Gamma ◽  
Antigen Processing ◽  
Antigen Presenting Cells ◽  
Class Ii ◽  
Invariant Chain ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Antigen Presenting

Presentation of exogenous protein antigens to T lymphocytes is based on the intersection of two complex pathways: (a) synthesis, assembly, and transport of major histocompatibility complex (MHC) class II-invariant chain complexes from the endoplasmic reticulum to a specialized endosomal compartment, and (b) endocytosis, denaturation, and proteolysis of antigens followed by loading of antigenic peptides onto newly synthesized MHC class II molecules. It is believed that expression of MHC class II heterodimers, invariant chain and human leukocyte antigen-DM is both necessary and sufficient to reconstitute a functional MHC class II loading compartment in antigen-presenting cells. Expression of each of these essential molecules is under the control of the MHC class II transactivator CIITA. Unexpectedly, however, whereas interferon gamma stimulation does confer effective antigen-processing function to nonprofessional antigen presenting cells, such as melanoma cells, expression of the CIITA transactivator alone is not sufficient. Activation of antigen-specific T cells thus requires additional CIITA-independent factor(s), and such factor(s) can be induced by interferon gamma.

scholarly journals Targeted Expression of Major Histocompatibility Complex (MHC) Class II Molecules Demonstrates that Dendritic Cells Can Induce Negative but Not Positive Selection of Thymocytes In Vivo

1997 ◽  
Vol 185 (3) ◽  
pp. 541-550 ◽  
Author(s):  
Thomas Brocker ◽  
Mireille Riedinger ◽  
Klaus Karjalainen
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Major Histocompatibility Complex ◽  
Positive Selection ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Selection Of

It is well established that lymphoid dendritic cells (DC) play an important role in the immune system. Beside their role as potent inducers of primary T cell responses, DC seem to play a crucial part as major histocompatibility complex (MHC) class II+ “interdigitating cells” in the thymus during thymocyte development. Thymic DC have been implicated in tolerance induction and also by some authors in inducing major histocompatibility complex restriction of thymocytes. Most of our knowledge about thymic DC was obtained using highly invasive and manipulatory experimental protocols such as thymus reaggregation cultures, suspension cultures, thymus grafting, and bone marrow reconstitution experiments. The DC used in those studies had to go through extensive isolation procedures or were cultured with recombinant growth factors. Since the functions of DC after these in vitro manipulations have been reported to be not identical to those of DC in vivo, we intended to establish a system that would allow us to investigate DC function avoiding artificial interferences due to handling. Here we present a transgenic mouse model in which we targeted gene expression specifically to DC. Using the CD11c promoter we expressed MHC class II I-E molecules specifically on DC of all tissues, but not on other cell types. We report that I-E expression on thymic DC is sufficient to negatively select I-E reactive CD4+ T cells, and to a less complete extent, CD8+ T cells. In contrast, if only DC expressed I-E in a class II–deficient background, positive selection of CD4+ T cells could not be observed. Thus negative, but not positive, selection events can be induced by DC in vivo.

scholarly journals Major histocompatibility complex-restricted recognition of retroviral superantigens by V beta 17+ T cells.

1992 ◽  
Vol 176 (1) ◽  
pp. 275-280 ◽  
Author(s):  
M A Blackman ◽  
F E Lund ◽  
S Surman ◽  
R B Corley ◽  
D L Woodland
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Major Histocompatibility ◽  
Direct Role ◽  
Histocompatibility Complex ◽  
Class Ii Mhc ◽  
Mhc Class Ii Molecules

It has been established that at least some V beta 17+ T cells interact with an endogenous superantigen encoded by the murine retrovirus, Mtv-9. To analyze the role of major histocompatibility complex (MHC) class II molecules in presenting the Mtv-9 encoded superantigen, vSAG-9 to V beta 17+ hybridomas, a panel of nine hybridomas was tested for their ability to respond to A20/2J (H-2d) and LBK (H-2a) cells which had been transfected with the vSAG-9 gene. Whereas some of the hybridomas recognized vSAG-9 exclusively in the context of H-2a, other hybridomas recognized vSAG-9 exclusively in the context of H-2d or in the context of both H-2d and H-2a. These results suggest that: (a) the class II MHC molecule plays a direct role in the recognition of retroviral superantigen by T cells, rather than serving simply as a platform for presentation; and, (b) it is likely that components of the TCR other than V beta are involved in the vSAG-9/TCR/class II interaction.

scholarly journals The Major Histocompatibility Complex of Old World Camels—A Synopsis

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1200 ◽  
Author(s):  
Plasil ◽  
Wijkmark ◽  
Elbers ◽  
Oppelt ◽  
Burger ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Mhc Class I ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Class I ◽  
Class Iii ◽  
Old World ◽  
Histocompatibility Complex ◽  
Mhc Class Iii ◽  
Antigen Presenting

This study brings new information on major histocompatibility complex (MHC) class III sub-region genes in Old World camels and integrates current knowledge of the MHC region into a comprehensive overview for Old World camels. Out of the MHC class III genes characterized, TNFA and the LY6 gene family showed high levels of conservation, characteristic for MHC class III loci in general. For comparison, an MHC class II gene TAP1, not coding for antigen presenting molecules but functionally related to MHC antigen presenting functions was studied. TAP1 had many SNPs, even higher than the MHC class I and II genes encoding antigen presenting molecules. Based on this knowledge and using new camel genomic resources, we constructed an improved genomic map of the entire MHC region of Old World camels. The MHC class III sub-region shows a standard organization similar to that of pig or cattle. The overall genomic structure of the camel MHC is more similar to pig MHC than to cattle MHC. This conclusion is supported by differences in the organization of the MHC class II sub-region, absence of functional DY genes, different organization of MIC genes in the MHC class I sub-region, and generally closer evolutionary relationships of camel and porcine MHC gene sequences analyzed so far.

scholarly journals Specificity of Effector T Lymphocytes in Autologous Graft-Versus-Host Disease: Role of the Major Histocompatibility Complex Class II Invariant Chain Peptide

Blood ◽  
1997 ◽  
Vol 89 (6) ◽  
pp. 2203-2209 ◽  
Author(s):  
Allan D. Hess ◽  
Emilie C. Bright ◽  
Christopher Thoburn ◽  
Georgia B. Vogelsang ◽  
Richard J. Jones ◽  
...  
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
T Lymphocytes ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Effector T Cells ◽  
Invariant Chain ◽  
Target Cells ◽  
Graft Versus Host ◽  
Histocompatibility Complex

Abstract Administration of the immunosuppressive drug cyclosporine after autologous bone marrow transplantation induces a systemic autoimmune syndrome resembling graft-versus-host disease (GVHD). This syndrome termed autologous GVHD has significant antitumor activity. Associated with autologous GVHD is the development of T lymphocytes that recognize major histocompatibility complex (MHC) class II determinants, including self. The present studies attempted to characterize and define the molecular specificity of the effector T lymphocytes in autologous GVHD induced in patients with metastatic breast cancer. The results suggest that the effector cells associated with human autologous GVHD are CD8+ T lymphocytes expressing the α/β T-cell receptor. Additional studies show that the effector T cells recognize MHC class II antigens in association with a peptide from the invariant chain (CLIP). Pretreatment of autologous lymphoblast target cells with anti-CLIP antibody completely blocked lysis mediated by autologous GVHD effector T cells. On the other hand, force loading this peptide markedly enhanced the susceptibility of the target cells to recognition by the autoreactive T cells. The recognition of the MHC class II CLIP complex may account for the novel specificity of the effector T cells associated with human autologous GVHD. Moreover, identification of the target peptide may allow for the development of novel immunotherapeutic strategies to enhance the antitumor efficacy of autologous GVHD.

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