Search results for "MHC restriction"
showing 10 items of 41 documents
Identification of transcripts of the T cell antigen receptor beta chain gene and major histocompatibility complex class II genes in antigen-presentin…
1988
The cloned murine cell line BK-BI-2.6.C6 has previously been shown to exhibit T cell characteristics, to synthesize and express MHC class II molecules, and to present protein antigens to antigen-dependent T cell clones. As a more definitive proof of the T-cell nature of these cells, transcripts of the rearranged T cell antigen receptor (TcR) beta gene were assessed by Northern blot analysis. BK-BI-2.6.C6 cells constitutively transcribe mRNA for the light chain of TcR and express the disulphide-linked alpha, beta TcR heterodimer at the cell surface. In addition mRNA for the polymorphic MHC class II subunits A alpha and A beta as well as for the invariant gamma chain were detected. BK-BI-2.6.…
Macrophages Escape Inhibition of Major Histocompatibility Complex Class I-Dependent Antigen Presentation by Cytomegalovirus
2000
ABSTRACTThe mouse cytomegalovirus (MCMV)m152- andm06-encoded glycoproteins gp40 and gp48, respectively, independently downregulate major histocompatibility complex (MHC) class I surface expression during the course of productive MCMV infection in fibroblasts. As a result, presentation of an immediate-early protein pp89-derived nonapeptide toH-2Ld-restricted CD8+cytotoxic T cells is completely prevented in fibroblasts. Here we demonstrate that MCMV-infected primary bone marrow macrophages and the macrophage cell line J774 constitutively present pp89 peptides during permissive MCMV infection to cytotoxic T lymphocytes (CTL). In contrast to fibroblasts, expression of them152andm06genes in macr…
Major histocompatibility complex class I-restricted activation of cloned T cells by a soluble protein in the absence of accessory cells.
1989
A T-cell clone, 10BK.1, was established from the draining lymph nodes of (B10 x B10.BR)F1 mice immunized with ovalbumin (OVA) according to standard protocols. Upon coculture with the antigen, 10BK.1 cells reacted by production of lymphokines and by proliferation despite the absence of additional antigen-presenting cells. These T cells do not express major histocompatibility complex (MHC) class II molecules on the cell surface as assessed on the basis of several criteria: by cytofluorometric analysis I-A and I-E determinants were not detectable; 10BK.1 cells could not act as antigen-presenting cells for long-term-cultured MHC class II-restricted T-cell clones; and monoclonal antibodies direc…
Requirements of Exogenous Protein Antigens for Presentation to CD4+ T lymphocytes By MHC Class II-Positive APC
1993
The antigen-specific activation of CD4-positive T helper cells depends on the recognition of a complex of MHC class II molecules and an antigen-derived peptide on the surface of antigen-presenting cells (APC). For most antigens generation of this MHC/peptide complex requires the uptake of the respective antigen by APC, followed by intracellular processing. The latter leads to suitable peptides of the antigen which are able to bind to MHC class ll-molecules. Subsequently the resulting complexes are transported to the cell surface. Evidence supporting this concept came mainly from the finding that agents such as chloroquine1, interfering with the function of endosomes and lysosomes, can block…
MHC-restricted T cell receptor signaling is required for αβ TCR replacement of the pre T cell receptor
2008
A developmental block is imposed on CD25(+)CD44(-) thymocytes at the beta-selection checkpoint in the absence of the pre T cell receptor (preTCR) alpha-chain, pTalpha. Early surface expression of a transgenic alphabeta TCR has been shown to partially circumvent this block, such that thymocytes progress to the CD4(+)CD8(+) double-positive stage. We wanted to analyze whether a restricting MHC element is required for alphabeta TCR-expressing double-negative (DN) thymocytes to overcome the developmental block in pTalpha-deficient animals. We used the HY-I knock-in model that endows thymocytes with alphabeta TCR expression in the DN compartment but has the advantage of physiological expression l…
CD8 T cell-evasive functions of human cytomegalovirus display pervasive MHC allele specificity, complementarity, and cooperativity.
2014
Abstract Immunoevasive proteins (“evasins”) of human CMV (HCMV) modulate stability and localization of MHC class I (MHC I) molecules, and their supply of antigenic peptides. However, it is largely unknown to what extent these evasins interfere with recognition by virus-specific CD8 T cells. We analyzed the recognition of HCMV-infected cells by a panel of CD8 T cells restricted through one of nine different MHC I allotypes. We employed a set of HCMV mutants deleted for three or all four of the MHC I modulatory genes US2, US3, US6, and US11. We found that different HCMV evasins exhibited different allotype-specific patterns of interference with CD8 T cell recognition of infected cells. In con…
Processing and MHC class I presentation of human cytomegalovirus pp65-derived peptides persist despite gpUS2–11-mediated immune evasion
2007
Immune control of human cytomegalovirus (HCMV) infection can be mediated by CD8+cytolytic T lymphocytes (CTL). Adoptive transfer of antiviral CTL confers protection against HCMV reactivation and disease. The tegument protein pp65 and the immediate-early 1 protein (IE1) are recognized to be major CTL targets, even though during productive infection the viral immunoevasion proteins gpUS2–11 act to suppress major histocompatibility complex (MHC) class I-restricted antigen presentation. Thus it was not clear how infected cells could be labelled with antigenic peptides in the face of immunoevasion. We show here that the immunodominant peptide pp65NLVwas presented by MHC class I in cells infected…
Analysis of the MHC Class I Antigen Presentation Machinery in Human Embryonal Carcinomas: Evidence for Deficiencies in TAP, LMP and MHC Class I Expre…
1998
The expression of the major histocompatibility complex (MHC) class I antigens is suppressed in early post-implantation embryonic cells as well as in embryonal carcinoma (EC) cells, but could be upregulated by treatment with interferon (IFN)-gamma or retinoic acid. In a number of human and murine tumours, defects in the expression of the different components of the MHC class I antigen processing machinery, such as the proteasomal subunits LMP-2 and LMP-7 and the peptide transporters TAP-1 and TAP-2, account for impaired MHC class I surface expression. Here, we analysed the constitutive and IFN-gamma regulated mRNA and protein expression of the LMP, TAP and MHC class I molecules in the human …
Bipartite regulation of different components of the MHC class I antigen-processing machinery during dendritic cell maturation
2001
Dendritic cells (DC) are professional antigen-presenting cells (APC) which proceed from immature to a mature stage during their final differentiation. Immature DC are highly effective in terms of antigen uptake and processing, whereas mature DC become potent immunostimulatory cells. Until now, the expression profiles of the major components of the MHC class I antigen-processing machinery (APM) during DC development have not been well characterized. In this study, the mRNA and protein expression levels of the IFN-gamma inducible proteasome subunits, of the proteasome activators PA28, and of key components required for peptide transport and MHC class I-peptide complex assembly have been evalu…
Features of TAP-independent MHC class I ligands revealed by quantitative mass spectrometry.
2008
TAP is responsible for transferring cytosolic peptides into the ER, where they can be loaded onto MHC molecules. Deletion of TAP results in a drastic reduction of MHC class I surface expression and alters the presented peptide pattern. This key molecule in antigen processing is tackled by several viruses and lost in some tumors, rendering the altered cells less vulnerable to T cell-based immune surveillance. Using the TAP-deficient cell line LCL721.174 and its TAP-expressing progenitor cell line LCL721.45, we identified and quantified more than 160 HLA ligands, 50 of which were presented TAP-independently. Peptides which were predominantly presented on the TAP-deficient LCL721.174 cell line…