Search results for "MHC Class II"

H2-M, a facilitator of MHC class II peptide loading, and its negative modulator H2-O are differentially expressed in response to proinflammatory cyto…

2000

H2-M is a major histocompatibility complex (MHC) class II-like molecule that catalyzes peptide binding to MHC class II molecules. Recently, the H2-O heterodimer, encoded by H2-Oa and H2-Ob in the MHC class II region, has been shown to be physically associated with H2-M in B cells and to downregulate H2-M function. Examination of H2-O expression in freshly isolated mouse organs revealed that H2-Oa- and H2-Ob-specific transcripts are present in both lymphoid and nonlymphoid tissues. To evaluate the gene regulation and functional impact of H2-O on antigen presentation, we examined the effects on MHCII, invariant chain (Ii), H2-M, and H2-O gene expression of interleukin (IL)-4, IL-10, and inter…

Isolation of Differentially Expressed Genes in Epidermal Langerhans Cells

1997

Epidermal Langerhans cells (LC) represent immature dendritic cells (DC) resident in the skin, which are not yet able to prime naive T cells1. In vitro cultivation of LC in the presence of keratinocytes, supplying survival and differentiation signals, induces maturation events in LC2. These are highlighted by the downregulation of the biosynthesis of MHC class II molecules3, by the upregulation of the surface expression of adhesion and costimulatory molecules like CD80, CD86, CD54 and CD584,5, and by the acquisition of a potent immunostimulatory capacity for T cells6. Mature LC are potent inducers of naive T cells. Thus LC represent an ideal model system to investigate the maturation of DC (…

Abstract A110: Mutant MHC class II epitopes drive therapeutic immune responses to cancer

2016

Abstract Mutations are regarded as ideal targets for cancer immunotherapy. As neoepitopes with strict lack of expression in any healthy tissue, they are expected to be safe and could bypass the central tolerance mechanisms. Recent advances in nucleic acid sequencing technologies have revolutionized the field of genomics, allowing the readily targeting of mutated neoantigens for personalized cancer vaccination. We demonstrated in three independent murine tumor models that a considerable fraction of non-synonymous cancer mutations is immunogenic and that unexpectedly the immunogenic mutanome is pre-dominantly recognized by CD4+ T cells. RNA vaccination with such MHC class II restricted immuno…

Effects of interferon gamma on the proliferation and modulation of cell-surface structures of human ovarian carcinoma cell lines.

1993

Platinum-containing regimens are very effective in the primary treatment of ovarian cancer. However, upon subsequent treatment most tumors develop multidrug resistance. The clinical application of biological response modifiers like interferon gamma (IFN gamma) in advanced ovarian cancer is therefore of increasing interest. Permanent ovarian cancer cell lines are suitable for investigating the mode of action and the potential clinical effectiveness of such response modifiers. IFN gamma is known to modulate many cellular functions. In this study it was compared for its antiproliferative and antigen-modulatory activity on the expression of tumor-associated (CA-125, HMFG, CEA) and major histoco…

Differential MHC class II component expression in HPV-positive cervical cancer cells: implication for immune surveillance.

2005

Effective eradication of human papillomavirus (HPV)-positive tumors may require CD8+ and CD4+ T-cell-mediated immune responses. Ectopic expression of MHC class II surface molecules has been described in the context of cervical cancer, but coexpression with other components of the MHC class II antigen presentation pathway has not been addressed. We have evaluated the MHC class II antigen presentation pathway in malignant squamous epithelium of HPV+ cervical cancer lesions by in situ costaining HLA-DR with CLIP or DMA/DMB. Cervical cancer cells exhibit 3 MHC class II phenotypes: (i) DR+/CLIP+ or DM+; (ii) DR+/CLIP- or DM-; and (iii) DR-/CLIP+ or DM+. The identical profile has been identified …

T-cell Receptor Therapy Targeting Mutant Capicua Transcriptional Repressor in Experimental Gliomas

2021

Abstract Purpose: Gliomas are intrinsic brain tumors with a high degree of constitutive and acquired resistance to standard therapeutic modalities such as radiotherapy and alkylating chemotherapy. Glioma subtypes are recognized by characteristic mutations. Some of these characteristic mutations have shown to generate immunogenic neoepitopes suitable for targeted immunotherapy. Experimental Design: Using peptide-based ELISpot assays, we screened for potential recurrent glioma neoepitopes in MHC-humanized mice. Following vaccination, droplet-based single-cell T-cell receptor (TCR) sequencing from established T-cell lines was applied for neoepitope-specific TCR discovery. Efficacy of intravent…

Cathepsin B in Antigen-Presenting Cells Controls Mediators of the Th1 Immune Response during Leishmania major Infection

2014

Resistance and susceptibility to Leishmania major infection in the murine model is determined by the capacity of the host to mount either a protective Th1 response or a Th2 response associated with disease progression. Previous reports involving the use of cysteine cathepsin inhibitors indicated that cathepsins B (Ctsb) and L (Ctsl) play important roles in Th1/Th2 polarization during L. major infection in both susceptible and resistant mouse strains. Although it was hypothesized that these effects are a consequence of differential patterns of antigen processing, the mechanisms underlying these differences were not further investigated. Given the pivotal roles that dendritic cells and macrop…

Biochemical analysis of class II antigens. Identification of a two- and a three-polypeptide chain complex of I-A locus equivalent molecules in the ra…

1983

The polypeptide chain composition of class II antigens from LEW rat spleen cells was studied utilizing cross-reactive mouse alloantiserum A. TH anti-A.TL (specificity anti-Iak) and the monoclonal antibodies MRC-OX6 and MRC-OX3 for immunoprecipitation. Two-dimensional gel mapping of A. TH anti-A. TL immunoprecipitates revealed that, as in the mouse, two groups of class II antigens exist corresponding to I-A and I-E locus equivalent structures. In the absence of reducing agents three monomeric chains α, 36 kDa (p36); γ, 33 kDa (p33); and β, 23 kDa (p23), were detected for I-A equivalent antigens, whereas I-E equivalent molecules separated into five monomeric chains: α, 37 kDa (p37); γ, 33 kDa…

Impact of thymus on the generation of immunocompetence and diversity of antigen-specific MHC-restricted cytotoxic T-lymphocyte precursors.

1981

Structure of MHC class I and class II cDNAs and possible immunodeficiency linked to class II expression in the Mexican axolotl

1998

Despite the fact that the axolotl (Ambystoma spp. a urodele amphibian) displays a large T-cell repertoire and a reasonable B-cell repertoire, its humoral immune response is slow (60 days), non-anamnestic, with a unique IgM class. The cytotoxic immune response is slow as well (21 days) with poor mixed lymphocyte reaction stimulation. Therefore, this amphibian can be considered as immunodeficient. The reason for this subdued immune response could be an altered antigenic presentation by major histocompatibility complex (MHC) molecules. This article summarizes our work on axolotl MHC genes. Class I genes have been characterized and the cDNA sequences show a good conservation of non-polymorphic …