Search results for "major histocompatibility complex"

Targeting p53, hdm2, and CD19: vaccination and immunologic strategies.

2000

Peptides presented by class I major histocompatibility complex (MHC) molecules and derived from normal self-proteins that are expressed at elevated levels by cells from a variety of human (Hu) malignancies provide, in theory, potential target antigens for a broad-spectrum, cytotoxic T lymphocyte (CTL)-based immunotherapy of cancer and hematologic malignancies. However, as such tumor- and leukemia-associated self-proteins are also expressed at low levels in some types of normal tissues, such as thymus, spleen and lymphohemopoietic cells, these self-MHC-self-peptide complexes may also represent thymic and/or peripheral tolerogens, thereby preventing immune responses. This is particularly true…

TAP off - tumors on

1997

Abstract The molecular characterization of T-cell-defined tumor-associated antigens has provided targets for cell-mediated immunotherapy for malignant diseases. The success of this strategy is negatively influenced by structural and functional abnormalities of major histocompatibility complex (MHC) class I molecules, which provide tumor cells with resistance to T-cell-mediated immune recognition. This article reviews the physiology of the MHC class I processing machinery and describes the deficiencies of this pathway in malignant cells.

In vivo γδ T Cell Priming to Mycobacterial Antigens by Primary Mycobacterium tuberculosis Infection and Exposure to Nonpeptidic Ligands

1999

The recognition of phosphorylated nonpeptidic microbial metabolites by Vγ9Vδ2 T cells does not appear to require the presence of MHC molecules or antigen processing, permitting rapid responses against microbial pathogens. These may constitute an important area of natural anti-infectious immunity. To provide evidence of their involvement in immune reactivities against mycobacteria, we measured the responsiveness of peripheral blood Vγ9Vδ2 T cells in children with primary Mycobacterium tuberculosis (MTB) infections. Peripheral blood mononuclear cells from 22 children with MTB infections and 16 positivity of tuberculin (PPD)-negative healthy children were exposed to nonpeptidic antigens in vit…

2014

Viral CD8 T-cell epitopes, represented by viral peptides bound to major histocompatibility complex class-I (MHC-I) glycoproteins, are often identified by “reverse immunology”, a strategy not requiring biochemical and structural knowledge of the actual viral protein from which they are derived by antigen processing. Instead, bioinformatic algorithms predicting the probability of C-terminal cleavage in the proteasome, as well as binding affinity to the presenting MHC-I molecules, are applied to amino acid sequences deduced from predicted open reading frames (ORFs) based on the genomic sequence. If the protein corresponding to an antigenic ORF is known, it is usually inferred that the kinetic …

Identification of epitopes of Mycobacterium tuberculosis 16-kDa protein recognized by human leukocyte antigen-A*0201 CD8(+) T lymphocytes.

2002

CD8(+) T cells could make an important contribution to protection against tuberculosis (TB), but the antigenic determinants recognized in the context of major histocompatibility complex class I molecules remain ill defined. Our aim was to identify nonamer peptides derived from the acr/16-kDa antigen. Two immunogenic peptides (p21-29 and p120-128) were identified by their ability to elicit cytotoxic CD8(+) T cells from juvenile patients recovering from TB. Epitope-specific recognition was demonstrated by the lysis of both Mycobacterium tuberculosis-infected and peptide-pulsed macrophages, the release of cytotoxic granules, and interferon-gamma and tumor necrosis factor-alpha production. CD8(…

An antigen-independent physiological activation pathway for L3T4+ T lymphocytes.

1987

The data presented in this report describe an antigen-independent activation pathway leading to reinduction of proliferation of class II major histocompatibility complex (MHC)-restricted murine T cell lines that after previous antigen-specific stimulation reverted to a resting state. Antigen-independent proliferation and interleukin 2 (IL2)-receptor expression occur in the presence of splenic accessory cells, exogenous IL2 and a soluble factor(s) provisionally termed T cell-stimulating factor(s) (TSF). Each of these components is essential for inducing growth. TSF is found in the supernatant of an autoreactive T cell line upon stimulation with syngeneic accessory cells. Neither TSF nor acce…

A TNF-α Promoter Polymorphism Is Associated with Juvenile Onset Psoriasis and Psoriatic Arthritis

1997

Tumor necrosis factor-α is considered to be one of the important mediators in the pathogenesis of psoriasis. A strong association of juvenile onset psoriasis with the major histocompatibility complex encoded HLA-Cw6 antigen has been reported but it is unclear whether Cw6 itself or a closely linked gene is involved in the pathogenesis. This study has focused on the association of promoter polymorphisms of the major histocompatibility complex encoded tumor necrosis factor-α gene with psoriasis and psoriatic arthritis. Tumor necrosis factor-α promoter polymorphisms were sought by sequence-specific oligonucleotide hybridization and by direct sequencing in Caucasian patients with juvenile onset …

Pathogenesis of autoimmune diseases associated with 8.1 ancestral haplotype: effect of multiple gene interactions.

2003

Genetic studies have shown that individuals with certain HLA alleles have a higher risk of specific autoimmune disease than those without these alleles. Particularly, the association in all Caucasian populations of an impressive number of autoimmune diseases with genes from the HLA-B8,DR3 haplotype that is part of the ancestral haplotype (AH) 8.1 HLA-A1, Cw7, B8, TNFAB*a2b3, TNFN*S, C2*C, Bf*s, C4A*Q0, C4B*1, DRB1*0301, DRB3*0101, DQA1*0501, DQB1*0201 has been reported by different research groups. This haplotype, the more common one in northern Europe, is also associated in healthy subjects with a number of immune system dysfunctions. It has been proposed that a small number of genes withi…

Detection of antigen-specific T-cells with MHC/peptide-tetramer-complexes

2002

Abstract Tetramer analysis is a novel technique in immunological research that has dramatically changed our knowledge of the immune response to viral and bacterial pathogens, to tumors and in autoimmune disease. Through the formation of major histocompatibility complex (MHC)/peptide-tetrameric complexes it can provide accurate counts of antigen-specific T-cells and it allows their phenotypical and functional analysis. We review the strengths of this method and use the analysis of peripheral blood lymphocytes (PBL) from a patient with melanoma as a paradigm for the detection of tetramer-binding T-cells. The implementation of tetramer-guided analysis in immunomonitoring allows the ex vivo tes…

Experimental confirmation of the 'protein traffic hypothesis' by routine diagnostic tests

2010

The 'protein traffic hypothesis' suggests that the inflammation associated with autoimmune disease, trauma and disturbances of blood circulation is the result of misguided protein trafficking. The hypothesis divides the antigen spectrum into an intracellular component and an extracellular component. While the intracellular component is recognised by MHC class-I molecules and is presented to CD8 T-lymphocytes, the extracellular component is recognised by MHC class-II molecules and is presented to CD4 T-lymphocytes. To test this hypothesis, CD4 and CD8 T-cell counts of 271 HIV-negative patients of the University Hospital, Mainz, Germany were examined retrospectively. The results corroborate t…