Abstract
Until about 1990 there was general consent about the assumption that only protein and peptide antigens have the capacity of CD4+ or CD8+ T-cell stimulation. Since about ten years evidence is now accumulating that carbohydratepeptide epitopes do play a role in classical MHC-mediated immune responses. This holds true for glycopeptides, where the glycan chain is short and not located at an anchor residue needed for MHC interaction. T-cell recognition of Oglycosylated peptides is potentially of high biomedical significance, because it can mediate the immune protection against microorganisms, the vaccination in anti-tumor therapies, but also some aspects of autoimmunity. The epithelial type 1 transmembrane mucin MUC1 is established as a marker for monitoring recurrence of breast cancer and is a promising target for immunotherapeutic strategies to treat cancer by active specific immunization. Natural human immune responses to the tumor-associated glycoforms of the mucin indicate that antibody reactivities are more directed to glycopeptide than to non-glycosylated peptide epitopes. To overcome the weak immunogenicity of the natural target, heavily O-glycosylated MUC1, the question was addressed whether O-linked glycans remain intact during processing in the MHC class II pathway and interfere with endosomal processing and peptide presentation. Attempts were made to define on a biochemical level the structural requirements for an efficient endosomal proteolysis catalyzed by cathepsin L in antigen-presenting cells. Evidence based on work with CD4+ T-hybridomas confirms that O-glycopeptides can be effectively presented to T-cells and that glycans can form integral parts of the TCR defined epitopes. Similar approaches are currently followed in the MHC class I pathway which aim at the identification of immunogenic glycopeptides generated by immunoproteasomes.
Keywords: MUC1, O-glycosylation, glycopeptides, processing, MHC presentation, glycopeptide-specific T cells, tumor vaccine
Current Protein & Peptide Science
Title: Immunology of O-Glycosylated Proteins: Approaches to the Design of a MUC1 Glycopeptide-Based Tumor Vaccine
Volume: 7 Issue: 4
Author(s): Franz-Georg Hanisch and Tanja Ninkovic
Affiliation:
Keywords: MUC1, O-glycosylation, glycopeptides, processing, MHC presentation, glycopeptide-specific T cells, tumor vaccine
Abstract: Until about 1990 there was general consent about the assumption that only protein and peptide antigens have the capacity of CD4+ or CD8+ T-cell stimulation. Since about ten years evidence is now accumulating that carbohydratepeptide epitopes do play a role in classical MHC-mediated immune responses. This holds true for glycopeptides, where the glycan chain is short and not located at an anchor residue needed for MHC interaction. T-cell recognition of Oglycosylated peptides is potentially of high biomedical significance, because it can mediate the immune protection against microorganisms, the vaccination in anti-tumor therapies, but also some aspects of autoimmunity. The epithelial type 1 transmembrane mucin MUC1 is established as a marker for monitoring recurrence of breast cancer and is a promising target for immunotherapeutic strategies to treat cancer by active specific immunization. Natural human immune responses to the tumor-associated glycoforms of the mucin indicate that antibody reactivities are more directed to glycopeptide than to non-glycosylated peptide epitopes. To overcome the weak immunogenicity of the natural target, heavily O-glycosylated MUC1, the question was addressed whether O-linked glycans remain intact during processing in the MHC class II pathway and interfere with endosomal processing and peptide presentation. Attempts were made to define on a biochemical level the structural requirements for an efficient endosomal proteolysis catalyzed by cathepsin L in antigen-presenting cells. Evidence based on work with CD4+ T-hybridomas confirms that O-glycopeptides can be effectively presented to T-cells and that glycans can form integral parts of the TCR defined epitopes. Similar approaches are currently followed in the MHC class I pathway which aim at the identification of immunogenic glycopeptides generated by immunoproteasomes.
Export Options
About this article
Cite this article as:
Hanisch Franz-Georg and Ninkovic Tanja, Immunology of O-Glycosylated Proteins: Approaches to the Design of a MUC1 Glycopeptide-Based Tumor Vaccine, Current Protein & Peptide Science 2006; 7 (4) . https://dx.doi.org/10.2174/138920306778018034
DOI https://dx.doi.org/10.2174/138920306778018034 |
Print ISSN 1389-2037 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5550 |
Call for Papers in Thematic Issues
Advancements in Proteomic and Peptidomic Approaches in Cancer Immunotherapy: Unveiling the Immune Microenvironment
The scope of this thematic issue centers on the integration of proteomic and peptidomic technologies into the field of cancer immunotherapy, with a particular emphasis on exploring the tumor immune microenvironment. This issue aims to gather contributions that illustrate the application of these advanced methodologies in unveiling the complex interplay ...read more
Artificial Intelligence for Protein Research
Protein research, essential for understanding biological processes and creating therapeutics, faces challenges due to the intricate nature of protein structures and functions. Traditional methods are limited in exploring the vast protein sequence space efficiently. Artificial intelligence (AI) and machine learning (ML) offer promising solutions by improving predictions and speeding up ...read more
Nutrition and Metabolism in Musculoskeletal Diseases
The musculoskeletal system consists mainly of cartilage, bone, muscles, tendons, connective tissue and ligaments. Balanced metabolism is of vital importance for the homeostasis of the musculoskeletal system. A series of musculoskeletal diseases (for example, sarcopenia, osteoporosis) are resulted from the dysregulated metabolism of the musculoskeletal system. Furthermore, metabolic diseases (such ...read more
Protein Folding, Aggregation and Liquid-Liquid Phase Separation
Protein folding, misfolding and aggregation remain one of the main problems of interdisciplinary science not only because many questions are still open, but also because they are important from the point of view of practical application. Protein aggregation and formation of fibrillar structures, for example, is a hallmark of a ...read more
Related Journals
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Organ- and Cell-Type Specific Delivery of Kinase Inhibitors: A Novel Approach in the Development of Targeted Drugs
Current Molecular Pharmacology Overcoming the Hurdles of Tumor Immunity by Targeting Regulatory Pathways in Innate and Adaptive Immune Cells
Current Pharmaceutical Design Use of Analogs of Peptide Hormones Conjugated to Cytotoxic Radicals for Chemotherapy Targeted to Receptors on Tumors
Current Drug Delivery NADPH Oxidases and Inflammatory Bowel Disease
Current Medicinal Chemistry Matrix Metalloproteinases and Colon Anastomosis Repair: A New Indication for Pharmacological Inhibition?
Mini-Reviews in Medicinal Chemistry Improved Drug Delivery System for Cancer Treatment by D-Glucose Conjugation with Eugenol From Natural Product
Current Drug Delivery Preface: A New Era of Nanoimmunology
Current Pharmaceutical Biotechnology The Complexity of Omega-3 Fatty Acid Modulation of Signaling Pathways Related to Pancreatic Cancer
Current Medicinal Chemistry Structure-Based Approach for the Discovery of Novel Selective Estrogen Receptor Modulators
Current Medicinal Chemistry Resistance of Cancer Cells to Targeted Therapies Through the Activation of Compensating Signaling Loops
Current Signal Transduction Therapy Cells of the Macrophage Lineage and their Role in the Pathogenesis of HIV-1 Infection: An Update
Medicinal Chemistry Reviews - Online (Discontinued) The Importance and Evolution of Radiation Dose in DCIS
Current Cancer Therapy Reviews Synthesis, Characterization of 4-Anilino-6,7-Dimethoxy Quinazoline Derivatives as Potential Anti-Angiogenic Agents
Anti-Cancer Agents in Medicinal Chemistry Potential Therapeutic Applications of Metal Compounds Directed Towards Hypoxic Tissues
Current Medicinal Chemistry Therapeutic Targeting of NLRP3 Inflammasomes by Natural Products and Pharmaceuticals: A Novel Mechanistic Approach for Inflammatory Diseases
Current Medicinal Chemistry DYRK1A: A Potential Drug Target for Multiple Down Syndrome Neuropathologies
CNS & Neurological Disorders - Drug Targets Src Family Kinases as Potential Therapeutic Targets for Malignancies and Immunological Disorders
Current Medicinal Chemistry Carbonic Anhydrase Inhibitors and the Management of Cancer
Current Topics in Medicinal Chemistry Bisphosphonate Anticancer Activity in Multiple Myeloma
Anti-Cancer Agents in Medicinal Chemistry Episcopic 3D Imaging Methods: Tools for Researching Gene Function
Current Genomics