scholarly journals MHC class I antigen cross-presentation mediated by PapMV nanoparticles in human antigen-presenting cells is dependent on autophagy

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0261987
Author(s):  
David Possamaï ◽  
Laïla-Aïcha Hanafi ◽  
Angélique Bellemare-Pelletier ◽  
Katia Hamelin ◽  
Paméla Thébault ◽  
...  
Keyword(s):  
Antigen Presentation ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Antigen Presenting Cells ◽  
Class I ◽  
Class I Mhc ◽  
Mhc I ◽  
Cross Presentation ◽  
Antigen Presenting ◽  
Papmv Nanoparticles

Nanoparticles made of the coat protein of papaya mosaic virus (PapMV) and a single-strand RNA were previously shown to be an efficient antigen presentation system for the trigger of cellular immunity. Engineering of PapMV nano with a cytotoxic T lymphocyte epitope was previously shown activating specific T lymphocytes through a proteasome-independent major histocompatibility complex class I (MHC-I) cross-presentation. In this study, we provide new insights into the mechanism of the MHC-I cross-presentation mediated by PapMV nanoparticles. We demonstrate that PapMV nanoparticles do not require the transporter associated with antigen presentation (TAP), but rather depend on lysosome acidification and cathepsin S protease activity for presentation of the T cell epitope. We have also linked the induction of autophagy with this vacuolar MHC-I cross-presentation process. Interestingly, autophagy is induced in antigen-presenting cells after PapMV nanoparticles exposure and inhibition of autophagy reduce MHC-I cross-presentation. This study demonstrates that autophagy is associated with TAP- and proteasome-independent MHC-I cross-presentation. A deeper understanding of the autophagy-dependent MHC-I cross-presentation will be useful in designing vaccination platforms that aim to trigger an efficient cytotoxic T lymphocyte response.

scholarly journals Bone Marrow–Derived Antigen-Presenting Cells Are Required for the Generation of Cytotoxic T Lymphocyte Responses to Viruses and Use Transporter Associated with Antigen Presentation (Tap)-Dependent and -Independent Pathways of Antigen Presentation

2000 ◽  
Vol 192 (8) ◽  
pp. 1143-1150 ◽  
Author(s):  
Luis J. Sigal ◽  
Kenneth L. Rock
Keyword(s):  
Bone Marrow ◽  
Antigen Presentation ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Antigen Presenting Cells ◽  
Lymphocytic Choriomeningitis ◽  
Ctl Response ◽  
Lymphocyte Responses ◽  
Antigen Presenting ◽  
Ctl Responses

Bone marrow (BM)-derived professional antigen-presenting cells (pAPCs) are required for the generation of cytotoxic T lymphocyte (CTL) responses to vaccinia virus and poliovirus. Furthermore, these BM-derived pAPCs require a functional transporter associated with antigen presentation (TAP). In this report we analyze the requirements for BM-derived pAPCs and TAP in the initiation of CTL responses to lymphocytic choriomeningitis virus (LCMV) and influenza virus (Flu). Our results indicate a requirement for BM-derived pAPCs for the CTL responses to these viruses. However, we found that the generation of CTLs to one LCMV epitope (LCMV nucleoprotein 396–404) was dependent on BM-derived pAPCs but, surprisingly, TAP independent. The study of the CTL response to Flu confirmed the existence of this BM-derived pAPC-dependent/TAP-independent CTL response and indicated that the TAP-independent pathway is ∼10–300-fold less efficient than the TAP-dependent pathway.

Virosome-mediated delivery of protein antigens in vivo: efficient induction of class I MHC-restricted cytotoxic T lymphocyte activity

Vaccine ◽  
2005 ◽  
Vol 23 (10) ◽  
pp. 1232-1241 ◽  
Author(s):  
Laura Bungener ◽  
Anke Huckriede ◽  
Arjan de Mare ◽  
Jacqueline de Vries-Idema ◽  
Jan Wilschut ◽  
...  
Keyword(s):  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Class I ◽  
Protein Antigens ◽  
Class I Mhc ◽  
Efficient Induction ◽  
Lymphocyte Activity

scholarly journals Variations in MHC class I antigen presentation and immunopeptidome selection pathways

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 1177
Author(s):  
Anita J. Zaitouna ◽  
Amanpreet Kaur ◽  
Malini Raghavan
Keyword(s):  
Cell Surface ◽  
Antigen Presentation ◽  
Surface Expression ◽  
Structural Features ◽  
Class I ◽  
Cell Surface Expression ◽  
Immune Recognition ◽  
Antigen Receptors ◽  
Class I Mhc ◽  
Mhc I

Major histocompatibility class I (MHC-I) proteins mediate immunosurveillance against pathogens and cancers by presenting antigenic or mutated peptides to antigen receptors of CD8+ T cells and by engaging receptors of natural killer (NK) cells. In humans, MHC-I molecules are highly polymorphic. MHC-I variations permit the display of thousands of distinct peptides at the cell surface. Recent mass spectrometric studies have revealed unique and shared characteristics of the peptidomes of individual MHC-I variants. The cell surface expression of MHC-I–peptide complexes requires the functions of many intracellular assembly factors, including the transporter associated with antigen presentation (TAP), tapasin, calreticulin, ERp57, TAP-binding protein related (TAPBPR), endoplasmic reticulum aminopeptidases (ERAPs), and the proteasomes. Recent studies provide important insights into the structural features of these factors that govern MHC-I assembly as well as the mechanisms underlying peptide exchange. Conformational sensing of MHC-I molecules mediates the quality control of intracellular MHC-I assembly and contributes to immune recognition by CD8 at the cell surface. Recent studies also show that several MHC-I variants can follow unconventional assembly routes to the cell surface, conferring selective immune advantages that can be exploited for immunotherapy.

scholarly journals Strictly transporter of antigen presentation (TAP)-dependent presentation of an immunodominant cytotoxic T lymphocyte epitope in the signal sequence of a virus protein.

1995 ◽  
Vol 182 (5) ◽  
pp. 1615-1619 ◽  
Author(s):  
J Hombach ◽  
H Pircher ◽  
S Tonegawa ◽  
R M Zinkernagel
Keyword(s):  
Antigen Presentation ◽  
Mhc Class I ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Signal Sequence ◽  
Class I ◽  
Signal Peptidase ◽  
Leader Peptide ◽  
Virus Protein ◽  
Mhc Class I Molecules

Peptides presented by major histocompatibility complex (MHC) class I molecules are derived from intracellularly synthesized proteins. Cytosolic proteins are fragmented into peptides, which are subsequently transported via the transporter of antigen presentation (TAP) into the endoplasmic reticulum (ER), where they bind to MHC class I molecules. We have investigated the requirements for MHC class I presentation of the immunodominant gp33 cytotoxic T lymphocyte epitope of the lymphocytic choriomeningitis virus. This epitope is located within the leader peptide of the virus glycoprotein. Such an epitope is expected to be presented in a TAP-independent manner, since it is released into the ER by signal peptidase. Taking advantage of TAP1-/- mice, however, we show both in vitro and in vivo that, after virus infection, the presentation of the gp33 epitope is strictly dependent on a functional TAP heterodimer. The results are discussed with respect to peptide trimming processes in the ER.

scholarly journals LC3 and NLRC5 Interaction Inhibits NLRC5-Mediated MHC Class I Antigen Presentation Pathway in Endometrial Cancer

2021 ◽  
Author(s):  
Lei Zhan ◽  
Junhui Zhang ◽  
Jing Zhang ◽  
Xiaojing Liu ◽  
Suding Zhu ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Antigen Presentation ◽  
Class I ◽  
Normal Endometrium ◽  
Tumor Immune Escape ◽  
Class I Mhc ◽  
Mhc I ◽  
Antigen Presentation Pathway ◽  
Presentation Pathway

Abstract Background: The major histocompatibility complex class I (MHC- I) transactivator, nucleotide binding oligomerization domain-like receptor family caspase recruitment domain containing 5 (NLRC5), serves as a target for immune evasion in many cancers, including endometrial cancer (EC). An inhibition of autophagy can contribute to immunotherapy by assisting the MHC-I-mediated antigen presentation in cancer. However, the underlying mechanism for autophagy-regulated MHC-I in EC remains unclear. Our study aimed to investigate the effect of autophagy on NLRC5 and MHC-I-mediated antigen presentation, and to identify the potential mechanisms underlying this process in EC.Methods: We examined the levels of autophagy and MHC-I genes by performing transmission electron microscopy (TEM), RNA-seq sequencing, western blotting, and qRT-PCR. The t-test, F-test, Kaplan-Meier analysis, and Pearson’s correlation analysis were used for statistical evaluations of tissue microarrays. Immunofluorescence staining, co-immunoprecipitation (CO-IP), and glutathione S-transferase (GST) pull-down assay were performed. HEC-1A, AN3CA, and Ishikawa EC cells were transfected designed, and the role of LC3 and NLRC5 in MHC-I-mediated antigen presentation in EC was further evaluated in a xenotransplantation model of HEC-1A cell line. Results: Autophagy was upregulated in EC endometrium as compared to that in normal endometrium. MHC I and NLRC5 expressions were lower in EC endometrium than in normal endometrium. Autophagy played a negative role in the MHC-I genes expression in vitro. Furthermore, a negative correlation was found between LC3 and NLRC5 levels, and LC3 interacted with NLRC5 to inhibit NLRC5-mediated MHC-I antigen presentation pathway in vitro and in vivo. Conclusion: An upregulation of LC3 in EC patients may contribute to tumor immune escape by restricting the NLRC5-mediated MHC-I antigen presentation pathway, suggesting that inhibiting LC3 and promoting NLRC5 may be a promising immunotherapy strategy in the management of EC.

Shaping the Repertoire of Cytotoxic T-Lymphocyte Responses: Explanation for the Immunodominance Effect Whereby Cytotoxic T Lymphocytes Specific for Immunodominant Antigens Prevent Recognition of Nondominant Antigens

Blood ◽  
1999 ◽  
Vol 93 (3) ◽  
pp. 952-962 ◽  
Author(s):  
Stéphane Pion ◽  
Gregory J. Christianson ◽  
Pierre Fontaine ◽  
Derry C. Roopenian ◽  
Claude Perreault
Keyword(s):  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Cell Receptor ◽  
Rapid Expansion ◽  
Class I ◽  
Tcr Signals ◽  
Lymphocyte Responses ◽  
Antigen Presenting ◽  
Dominant Epitope

The immunodominance effect, whereby the presence of immunodominant epitopes prevents recognition of nondominant determinants presented on the same antigen-presenting cell (APC) considerably restricts the repertoire of cytotoxic T lymphocyte (CTL) responses. To elucidate the molecular basis of the immunodominance effect, we compared the interactions of a dominant (B6dom1) and a nondominant epitope (H-Y) with their restricting class I molecule (H2-Db), and their ability to trigger cognate CTLs. We found that B6dom1/Db complexes behaved as optimal T-cell receptor (TCR) ligands and triggered a more rapid in vivo expansion of cognate CTLs than H-Y/Db complexes. The superiority of the dominant epitope was explained by its high cell surface density (1,012 copies/cell for B6dom1v 10 copies/cell for H-Y) and its optimal affinity for cognate TCRs. Based on these results, we conclude that dominant class I–associated epitopes are those that have optimal ability to trigger TCR signals in CTLs. We propose that the rapid expansion of CTLs specific for dominant antigens should enable them to compete more successfully than other CTLs for occupancy of the APC surface.

scholarly journals Hybrid antibody mediated veto of cytotoxic T lymphocyte responses.

1996 ◽  
Vol 183 (5) ◽  
pp. 1973-1980 ◽  
Author(s):  
Y Qi ◽  
R Berg ◽  
M A Singleton ◽  
J E Debrick ◽  
U D Staerz
Keyword(s):  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Class I ◽  
Cell Populations ◽  
Immune Functions ◽  
Class I Mhc ◽  
Cd8 Cells ◽  
Inhibitory Function ◽  
Veto Cells ◽  
Hybrid Antibody

Strategies are being sought that allow the induction of specific tolerance to allogeneic transplants without affecting other immune functions. The so-called veto effect has been described as one such technology where CD8+ cells suppress responses of class I MHC-restricted T-lymphocyte precursors to antigens expressed by those CD8+ veto cells. Yet, veto inhibition will not be able to provide complete tolerance to allogeneic grafts since it only operates on cell populations that express CD8. Other types of cells prevalent in most organs express different tissue-specific antigens that are recognized by alloreactive T-cells. Therefore, complete tolerance to an allogeneic transplant can only be achieved if all cellular components within the graft acquire the immune-inhibitory function. Here, we studied whether the veto effect could be exploited for this purpose nevertheless. We produced a hybrid antibody (HAb) combining a mAb specific for a class I MHC molecule with a soluble CD8 molecule. We found that this HAb specifically and effectively transferred veto inhibition to different stimulator cell populations. Thus, we have developed a strategy that promises to selectively and completely tolerize graft-specific CTLs without affecting normal immune responses.

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