The ABCs of Immunology: Structure and Function of TAP, the Transporter Associated with Antigen Processing

Physiology ◽  
2004 ◽  
Vol 19 (4) ◽  
pp. 216-224 ◽  
Author(s):  
Rupert Abele ◽  
Robert Tampé
Keyword(s):  
Antigen Processing ◽  
Cytotoxic T Cells ◽  
Peptide Delivery ◽  
Structure And Function ◽  
Transformed Cells ◽  
Tumor Escape ◽  
Mhc I ◽  
Histocompatibility Complex ◽  
Peptide Loading ◽  
And Function

The transporter associated with antigen processing (TAP) is essential for peptide delivery from the cytosol into the lumen of the endoplasmic reticulum (ER), where these peptides are loaded on major histocompatibility complex (MHC) I molecules. Loaded MHC I leave the ER and display their antigenic cargo on the cell surface to cytotoxic T cells. Subsequently, virus-infected or malignantly transformed cells can be eliminated. Here we discuss the structure, function, and mechanism of TAP as a central part of the peptide-loading complex. Furthermore, aspects of virus and tumor escape strategies are presented.

The transporter associated with antigen processing: a key player in adaptive immunity

2015 ◽  
Vol 396 (9-10) ◽  
pp. 1059-1072 ◽  
Author(s):  
Sabine Eggensperger ◽  
Robert Tampé
Keyword(s):  
Adaptive Immunity ◽  
Antigen Processing ◽  
Viral Infections ◽  
Cytotoxic T Cells ◽  
Adaptive Immune System ◽  
Molecular Transport ◽  
Antigenic Peptides ◽  
Mhc I ◽  
Peptide Loading ◽  
Primary Focus

Abstract The adaptive immune system co-evolved with sophisticated pathways of antigen processing for efficient clearance of viral infections and malignant transformation. Antigenic peptides are primarily generated by proteasomal degradation and translocated into the lumen of the endoplasmic reticulum (ER) by the transporter associated with antigen processing (TAP). In the ER, peptides are loaded onto major histocompatibility complex I (MHC I) molecules orchestrated by a multisubunit peptide-loading complex (PLC). Peptide-MHC I complexes are targeted to the cell surface for antigen presentation to cytotoxic T cells, which eventually leads to the elimination of virally infected or malignantly transformed cells. Here, we review MHC I mediated antigen processing with a primary focus on the function and structural organization of the heterodimeric ATP-binding cassette (ABC) transporter TAP1/2. We discuss recent data on the molecular transport mechanism of the antigen translocation complex with respect to structural and biochemical information of other ABC exporters. We further summarize how TAP provides a scaffold for the assembly of the macromolecular PLC, thereby coupling peptide translocation with MHC I loading. TAP inhibition by distinct viral evasins highlights the important role of TAP in adaptive immunity.

scholarly journals Assembly and Function of the Major Histocompatibility Complex (MHC) I Peptide-loading Complex Are Conserved Across Higher Vertebrates

2014 ◽  
Vol 289 (48) ◽  
pp. 33109-33117 ◽  
Author(s):  
Andreas Hinz ◽  
Johanna Jedamzick ◽  
Valentina Herbring ◽  
Hanna Fischbach ◽  
Jessica Hartmann ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Major Histocompatibility ◽  
Mhc I ◽  
Histocompatibility Complex ◽  
Peptide Loading ◽  
And Function

scholarly journals Light control of the peptide-loading complex synchronizes antigen translocation and MHC I trafficking

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Jamina Brunnberg ◽  
Valentina Herbring ◽  
Esteban Günther Castillo ◽  
Heike Krüger ◽  
Ralph Wieneke ◽  
...  
Keyword(s):  
Antigen Presentation ◽  
Antigen Processing ◽  
Adaptive Immune Response ◽  
Class I Mhc ◽  
Mhc I ◽  
Atp Binding Site ◽  
Histocompatibility Complex ◽  
Peptide Loading ◽  
Cellular Pathways ◽  
Cancerous Cells

AbstractAntigen presentation via major histocompatibility complex class I (MHC I) molecules is essential to mount an adaptive immune response against pathogens and cancerous cells. To this end, the transporter associated with antigen processing (TAP) delivers snippets of the cellular proteome, resulting from proteasomal degradation, into the ER lumen. After peptide loading and editing by the peptide-loading complex (PLC), stable peptide-MHC I complexes are released for cell surface presentation. Since the process of MHC I trafficking is poorly defined, we established an approach to control antigen presentation by introduction of a photo-caged amino acid in the catalytic ATP-binding site of TAP. By optical control, we initiate TAP-dependent antigen translocation, thus providing new insights into TAP function within the PLC and MHC I trafficking in living cells. Moreover, this versatile approach has the potential to be applied in the study of other cellular pathways controlled by P-loop ATP/GTPases.

scholarly journals The Role of HLA-G in Tumor Escape: Manipulating the Phenotype and Function of Immune Cells

2020 ◽  
Vol 10 ◽  
Author(s):  
Lu Liu ◽  
Lijun Wang ◽  
Lihong Zhao ◽  
Chen He ◽  
Ganlu Wang
Keyword(s):  
T Cells ◽  
Tumor Immunity ◽  
Immune Cells ◽  
Human Leukocyte ◽  
Therapeutic Benefit ◽  
Tumor Escape ◽  
Class I Mhc ◽  
Mhc I ◽  
Suppressive Phenotype ◽  
And Function

Human leukocyte antigen-G (HLA-G) is a non-classical major histocompatibility complex class I (MHC I) molecule, and under physiological conditions, its expression is strictly restricted to the maternal–fetal interface and immune-privileged organs where HLA-G is expected to contribute to establishment and maintenance of immune tolerance. However, the expression of HLA-G has been found in various types of tumors, and the level of its expression frequently correlates with high-grade histology and poor prognosis, raising the possibility that it may play a negative role in tumor immunity. ILT2 and ILT4, present on a broad of immune cells, have been identified as the main receptors engaging HLA-G, and their interactions have been found to allow the conversion of effectors like NK cells and T cells to anergic or unresponsive state, activated DCs to tolerogenic state, and to drive the differentiation of T cells toward suppressive phenotype. Therefore, tumors can employ HLA-G to modulate the phenotype and function of immune cells, allowing them to escape immune attack. In this review, we discuss the mechanism underlying HLA-G expression and function, its role played in each step of the tumor-immunity cycle, as well as the potential to target it for therapeutic benefit.

scholarly journals The transporter associated with antigen processing TAP: structure and function

FEBS Letters ◽  
1999 ◽  
Vol 464 (3) ◽  
pp. 108-112 ◽  
Author(s):  
Brigitte Lankat-Buttgereit ◽  
Robert Tampé
Keyword(s):  
Antigen Processing ◽  
Structure And Function ◽  
And Function

scholarly journals Physical and Functional Association of the Major Histocompatibility Complex Class I Heavy Chain α3 Domain with the Transporter Associated with Antigen Processing

1998 ◽  
Vol 187 (6) ◽  
pp. 865-874 ◽  
Author(s):  
Kimary Kulig ◽  
Dipankar Nandi ◽  
Igor Bacik ◽  
John J. Monaco ◽  
Stanislav Vukmanovic
Keyword(s):  
Mhc Class Ii ◽  
Heavy Chain ◽  
Antigen Processing ◽  
Surface Expression ◽  
Class I ◽  
Antigenic Peptides ◽  
Histocompatibility Complex ◽  
Cytoplasmic Proteins ◽  
Peptide Loading ◽  
Er Targeting

CD8+ T lymphocytes recognize antigens as short, MHC class I-associated peptides derived by processing of cytoplasmic proteins. The transporter associated with antigen processing translocates peptides from the cytosol into the ER lumen, where they bind to the nascent class I molecules. To date, the precise location of the class I-TAP interaction site remains unclear. We provide evidence that this site is contained within the heavy chain α3 domain. Substitution of a 15 amino acid portion of the H-2Db α3 domain (aa 219-233) with the analogous MHC class II (H-2IAd) β2 domain region (aa 133-147) results in loss of surface expression which can be partially restored upon incubation at 26°C in the presence of excess peptide and β2-microglobulin. Mutant H-2Db (Db219-233) associates poorly with the TAP complex, and cannot present endogenously-derived antigenic peptides requiring TAP-dependent translocation to the ER. However, this presentation defect can be overcome through use of an ER targeting sequence which bypasses TAP-dependent peptide translocation. Thus, the α3 domain serves as an important site of interaction (directly or indirectly) with the TAP complex and is necessary for TAP-dependent peptide loading and class I surface expression.

scholarly journals Presentation of Toxoplasma gondii Antigens via the Endogenous Major Histocompatibility Complex Class I Pathway in Nonprofessional and Professional Antigen-Presenting Cells

2007 ◽  
Vol 75 (11) ◽  
pp. 5200-5209 ◽  
Author(s):  
Florence Dzierszinski ◽  
Marion Pepper ◽  
Jason S. Stumhofer ◽  
David F. LaRosa ◽  
Emma H. Wilson ◽  
...  
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
Antigen Processing ◽  
Cell Types ◽  
T Cell Response ◽  
Complex Class ◽  
Mhc I ◽  
Histocompatibility Complex ◽  
Antigen Presenting

ABSTRACT Challenge with the intracellular protozoan parasite Toxoplasma gondii induces a potent CD8+ T-cell response that is required for resistance to infection, but many questions remain about the factors that regulate the presentation of major histocompatibility complex class I (MHC-I)-restricted parasite antigens and about the role of professional and nonprofessional accessory cells. In order to address these issues, transgenic parasites expressing ovalbumin (OVA), reagents that track OVA/MHC-I presentation, and OVA-specific CD8+ T cells were exploited to compare the abilities of different infected cell types to stimulate CD8+ T cells and to define the factors that contribute to antigen processing. These studies reveal that a variety of infected cell types, including hematopoietic and nonhematopoietic cells, are capable of activating an OVA-specific CD8+ T-cell hybridoma, and that this phenomenon is dependent on the transporter associated with antigen processing and requires live T. gondii. Several experimental approaches indicate that T-cell activation is a consequence of direct presentation by infected host cells rather than cross-presentation. Surprisingly, nonprofessional antigen-presenting cells (APCs) were at least as efficient as dendritic cells at activating this MHC-I-restricted response. Studies to assess whether these cells are involved in initiation of the CD8+ T-cell response to T. gondii in vivo show that chimeric mice expressing MHC-I only in nonhematopoietic compartments are able to activate OVA-specific CD8+ T cells upon challenge. These findings associate nonprofessional APCs with the initial activation of CD8+ T cells during toxoplasmosis.

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