Abstract
In humans, major histocompatibility complex (MHC) class I molecules comprise the classical (class Ia) human leukocyte antigens (HLA)-A, -B, and -C, and the non-classical (class Ib) HLA-E, -F, -G and – H (HFE) molecules. The best-characterized MHC class Ib molecule is HLA-E. HLA-E was first described as a non-polymorphic ligand of the CD94/NKG2 receptors expressed mainly by natural killer (NK) cells and its role was thus confined to the regulation of NK cell function. Therefore, interaction of HLA-E with the CD94/NKG2 receptors can result in either inhibition or activation of NK cells, depending on the peptide presented and on the NKG2 receptor CD94 is associated with. Thus, CD94/NKG2A functions as an inhibitory receptor, whereas CD94/NKG2C functions as an activating receptor. However, recent evidences obtained by our group and others indicated that HLA-E represents a novel restriction element for ab Tcell receptor (TCR)-mediated recognition. Although HLA-E displays a selective preference for nonameric peptides derived from the leader sequences of various HLA class I alleles, several reports showed that it can also present “noncanonical” peptides derived from both stress-related and pathogen-associated proteins. Because HLA-E displays binding specificity for innate CD94/NKG2 receptors but also has the features of an antigen-presenting molecule - including the ability to be recognized by ab T cells – it does appear that this MHC class Ib molecule plays an important role in both natural and acquired immune responses.
Keywords: HLA-E, natural killer cells, CD94/NKG2 receptors, human cytomegalovirus, gpUL40, ab TCR, alloreactivity, Graft-versus-host disease, graft rejection
Current Pharmaceutical Design
Title: HLA-E and HLA-E-Bound Peptides: Recognition by Subsets of NK and T Cells
Volume: 15 Issue: 28
Author(s): Gabriella Pietra, Chiara Romagnani, Lorenzo Moretta and Maria Cristina Mingari
Affiliation:
Keywords: HLA-E, natural killer cells, CD94/NKG2 receptors, human cytomegalovirus, gpUL40, ab TCR, alloreactivity, Graft-versus-host disease, graft rejection
Abstract: In humans, major histocompatibility complex (MHC) class I molecules comprise the classical (class Ia) human leukocyte antigens (HLA)-A, -B, and -C, and the non-classical (class Ib) HLA-E, -F, -G and – H (HFE) molecules. The best-characterized MHC class Ib molecule is HLA-E. HLA-E was first described as a non-polymorphic ligand of the CD94/NKG2 receptors expressed mainly by natural killer (NK) cells and its role was thus confined to the regulation of NK cell function. Therefore, interaction of HLA-E with the CD94/NKG2 receptors can result in either inhibition or activation of NK cells, depending on the peptide presented and on the NKG2 receptor CD94 is associated with. Thus, CD94/NKG2A functions as an inhibitory receptor, whereas CD94/NKG2C functions as an activating receptor. However, recent evidences obtained by our group and others indicated that HLA-E represents a novel restriction element for ab Tcell receptor (TCR)-mediated recognition. Although HLA-E displays a selective preference for nonameric peptides derived from the leader sequences of various HLA class I alleles, several reports showed that it can also present “noncanonical” peptides derived from both stress-related and pathogen-associated proteins. Because HLA-E displays binding specificity for innate CD94/NKG2 receptors but also has the features of an antigen-presenting molecule - including the ability to be recognized by ab T cells – it does appear that this MHC class Ib molecule plays an important role in both natural and acquired immune responses.
Export Options
About this article
Cite this article as:
Pietra Gabriella, Romagnani Chiara, Moretta Lorenzo and Mingari Cristina Maria, HLA-E and HLA-E-Bound Peptides: Recognition by Subsets of NK and T Cells, Current Pharmaceutical Design 2009; 15 (28) . https://dx.doi.org/10.2174/138161209789105207
DOI https://dx.doi.org/10.2174/138161209789105207 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- 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
- Announcements
Related Articles
-
Synthetic and Biological Vesicular Nano-Carriers Designed for Gene Delivery
Current Pharmaceutical Design Targeting Tumor Necrosis Factor-α in the Therapy of Psoriasis
Current Drug Targets - Inflammation & Allergy A Novel Monoclonal Antibody Against the C-terminus of β-Tubulin Recognizes Endocytic Organelles in Trypanosoma cruzi
Protein & Peptide Letters Alcohol and the Cardiovascular System: A Double-Edged Sword
Current Pharmaceutical Design Pharmacological Inhibition of the Bcl-2 Family of Apoptosis Regulators as Cancer Therapy
Current Molecular Pharmacology Stem Cells and Nanoparticles in Therapy
Nanoscience & Nanotechnology-Asia Sydnones: A Brief Review
Mini-Reviews in Medicinal Chemistry Muscarinic Receptors as Targets for Metronomic Therapy in Breast Cancer
Current Pharmaceutical Design Solvent-Free and Self-Catalyzed Three-Component Synthesis of Diversely Substituted Pyrazolo[1,4]thiazepinones of Potential Antitumor Activity
Current Organic Synthesis Prolylcarboxypeptidase Gene Expression in the Heart and Kidney: Effects of Obesity and Diabetes
Cardiovascular & Hematological Agents in Medicinal Chemistry Identification of HDACs Inhibitor E14 Metabolites Appeared in Rat Plasma, Feces and Urine by UPLC-QTOF-MS/MS
Current Pharmaceutical Analysis New Robotic Technologies in Cancer Colon Screening
Clinical Cancer Drugs Recent efforts toward the development of peptide secondary structure mimetics at Molecumetics Ltd. for the discoveries of new drug candidates utilizing combinatorial chemistry with solid phase synthesis are described
Combinatorial Chemistry & High Throughput Screening The Endothelial-Mesenchymal Transition (EndMT) and Tissue Regeneration
Current Stem Cell Research & Therapy Genomic Variations Affecting Biological Effects of Statins
Current Drug Metabolism Impact of SINEs and LINEs on the Mammalian Genome
Current Genomics Predicting Chemotherapy Sensitivity Profiles for Breast Cancer Cell Lines with and Without Stem Cell-Like Features
Current Signal Transduction Therapy Synthesis and Preliminary Evaluation of 5-[18F]fluoroleucine
Current Radiopharmaceuticals Mechanisms of CTLA-4-Ig in Tolerance Induction
Current Pharmaceutical Design A Critical Transcription Factor NF-κB as a Cancer Therapeutic Target and its Inhibitors as Cancer Treatment Options
Current Medicinal Chemistry