scholarly journals The C Terminus of the Nucleoprotein of Influenza A Virus Delivers Antigens Transduced by Tat to the trans-Golgi Network and Promotes an Efficient Presentation through HLA Class I

2005 ◽  
Vol 79 (24) ◽  
pp. 15537-15546 ◽  
Author(s):  
Francesca Bettosini ◽  
Maria Teresa Fiorillo ◽  
Adriana Magnacca ◽  
Laura Leone ◽  
Maria Rosaria Torrisi ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Antigen Processing ◽  
Immune Surveillance ◽  
Hla Class I ◽  
Class I ◽  
Amino Acid Region ◽  
Hla Class I Molecules ◽  
C Terminus ◽  
Golgi Network

ABSTRACT Cytotoxic T lymphocytes (CTLs) are the most powerful weapon of the immune system to eliminate cells infected by intracellular parasites or tumors. However, very often, escape mechanisms overcome CTL immune surveillance by impairing the classical HLA class I antigen-processing pathway. Here, we describe a strategy for CTL activation based on the ability of Tat to mediate transcellular delivery of viral proteins encompassing HLA class I-restricted epitopes. In this system, the recombinant protein TAT-NpFlu containing the transduction domain of Tat of human immunodeficiency virus type 1 fused to the amino acid region 301 to 498 of the nucleoprotein of influenza A virus is proven to sensitize different human cells to lysis by HLA-B27-restricted, Flu 383-391-specific CTL lines. The fusion protein is processed very effectively, since a comparable biological effect is obtained with an amount of protein between 1 and 2 orders of magnitude lower than that of the synthetic peptide. Interestingly, while part of TAT-NpFlu undergoes fast and productive cleavage, a large amount of it remains intact for up to 24 h. Confocal microscopy shows that TAT-NpFlu accumulates in the trans-Golgi network (TGN), where it starts to be detectable 1 h after transduction. Using TAT-NpFlu mutants and hybrid constructs, we demonstrate that enrichment in the TGN occurs only when the carboxy-terminal region of NpFlu (amino acids 400 to 498) is present. These data disclose an unconventional route for presentation of epitopes restricted for HLA class I molecules.

scholarly journals Antigen processing for MHC class I restricted presentation of exogenous influenza A virus nucleoprotein by B-lymphoblastoid cells

2001 ◽  
Vol 125 (3) ◽  
pp. 423-431 ◽  
Author(s):  
J. T. M. Voeten ◽  
G. F. Rimmelzwaan ◽  
N. J. Nieuwkoop ◽  
R. A. M. Fouchier ◽  
A. D. M. E. Osterhaus
Keyword(s):  
Mhc Class I ◽  
Influenza A Virus ◽  
Influenza A ◽  
Antigen Processing ◽  
Class I ◽  
Lymphoblastoid Cells

scholarly journals Expression of HLA class I molecules and the transporter associated with antigen processing in hepatocellular carcinoma

Hepatology ◽  
1996 ◽  
Vol 23 (5) ◽  
pp. 1181-1188 ◽  
Author(s):  
K Kurokohchi ◽  
M Carrington ◽  
D L Mann ◽  
T B Simonis ◽  
M A Alexander-Miller ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Antigen Processing ◽  
Hla Class I ◽  
Class I ◽  
Hla Class I Molecules

scholarly journals A Viral, Transporter Associated with Antigen Processing (TAP)-independent, High Affinity Ligand with Alternative Interactions Endogenously Presented by the Nonclassical Human Leukocyte Antigen E Class I Molecule

2012 ◽  
Vol 287 (42) ◽  
pp. 34895-34903 ◽  
Author(s):  
Elena Lorente ◽  
Susana Infantes ◽  
David Abia ◽  
Eilon Barnea ◽  
Ilan Beer ◽  
...  
Keyword(s):  
Human Leukocyte Antigen ◽  
Antigen Processing ◽  
Human Leukocyte ◽  
Hla Class I ◽  
Class I ◽  
Structural Motif ◽  
Leukocyte Antigen ◽  
High Affinity ◽  
Hla Class I Molecules ◽  
Infected Cells

The transporter associated with antigen processing (TAP) enables the flow of viral peptides generated in the cytosol by the proteasome and other proteases to the endoplasmic reticulum, where they complex with nascent human leukocyte antigen (HLA) class I. Later, these peptide-HLA class I complexes can be recognized by CD8+ lymphocytes. Cancerous cells and infected cells in which TAP is blocked, as well as individuals with unusable TAP complexes, are able to present peptides on HLA class I by generating them through TAP-independent processing pathways. Here, we identify a physiologically processed HLA-E ligand derived from the D8L protein in TAP-deficient vaccinia virus-infected cells. This natural high affinity HLA-E class I ligand uses alternative interactions to the anchor motifs previously described to be presented on nonclassical HLA class I molecules. This octameric peptide was also presented on HLA-Cw1 with similar binding affinity on both classical and nonclassical class I molecules. In addition, this viral peptide inhibits HLA-E-mediated cytolysis by natural killer cells. Comparison between the amino acid sequences of the presenting HLA-E and HLA-Cw1 alleles revealed a shared structural motif in both HLA class molecules, which could be related to their observed similar cross-reactivity affinities. This motif consists of several residues located on the floor of the peptide-binding site. These data expand the role of HLA-E as an antigen-presenting molecule.

Analysis of natural killer cells in TAP2-deficient patients: expression of functional triggering receptors and evidence for the existence of inhibitory receptor(s) that prevent lysis of normal autologous cells

Blood ◽  
2002 ◽  
Vol 99 (5) ◽  
pp. 1723-1729 ◽  
Author(s):  
Massimo Vitale ◽  
Jacques Zimmer ◽  
Roberta Castriconi ◽  
Daniel Hanau ◽  
Lionel Donato ◽  
...  
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Antigen Processing ◽  
Nk Cell ◽  
Hla Class I ◽  
Surface Expression ◽  
Class I ◽  
Inhibitory Receptor ◽  
Surface Receptors ◽  
Hla Class I Molecules

Natural killer (NK) cells are characterized by the ability to kill cells that lack HLA class I molecules while sparing autologous normal (HLA class I+) cells. However, patients with transporter-associated antigen processing (TAP) deficiency, though displaying strong reductions of HLA class I surface expression, in most instances do not experience NK-mediated autoimmune phenomena. A possible mechanism by which TAP−/− NK cells avoid autoreactivity against autologous HLA class I–deficient cells could be based on either quantitative or qualitative defects of surface receptors involved in NK cell triggering. In this study we show that NK cells derived from 2 patients with TAP2−/− express normal levels of all known triggering receptors. As revealed by the analysis of polyclonal and clonal NK cells, these receptors display normal functional capabilities and allow the killing of a panel of NK-susceptible targets, including autologous B-LCLs. On the other hand, TAP2−/− NK cells were unable to kill either allogeneic (HLA class I+) or autologous (HLA class I− ) phytohemagglutinin (PHA) blasts even in the presence of anti-HLA class I monoclonal antibody. These data suggest that TAP2−/− NK cells express still unknown inhibitory receptor(s) capable of down-regulating the NK cell cytotoxicity on binding to surface ligand(s) expressed by T cell blasts. Functional analyses, both at the polyclonal and at the clonal level, are consistent with the concept that the putative inhibitory receptor is expressed by virtually all TAP2−/− NK cells, whereas it is present only in rare NK cells from healthy persons. Another possibility would be that TAP2−/− NK cells are missing a still unidentified triggering receptor involved in NK cell-mediated killing of PHA blasts.

scholarly journals Acid Stripping after Infection Improves the Detection of Viral HLA Class I Natural Ligands Identified by Mass Spectrometry

2021 ◽  
Vol 22 (19) ◽  
pp. 10503
Author(s):  
Elena Lorente ◽  
Miguel Marcilla ◽  
Patricia G. de la Sota ◽  
Adriana Quijada-Freire ◽  
Carmen Mir ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Virus Infection ◽  
High Throughput ◽  
Antigen Processing ◽  
Hla Class I ◽  
T Cell Response ◽  
Class I ◽  
Hla Class I Molecules ◽  
Infected Cells ◽  
Hla Ligandome

Identification of a natural human leukocyte antigen (HLA) ligandome is a key element to understand the cellular immune response. Advanced high throughput mass spectrometry analyses identify a relevant, but not complete, fraction of the many tens of thousands of self-peptides generated by antigen processing in live cells. In infected cells, in addition to this complex HLA ligandome, a minority of peptides from degradation of the few proteins encoded by the viral genome are also bound to HLA class I molecules. In this study, the standard immunopeptidomics strategy was modified to include the classical acid stripping treatment after virus infection to enrich the HLA ligandome in virus ligands. Complexes of HLA-B*27:05-bound peptide pools were isolated from vaccinia virus (VACV)-infected cells treated with acid stripping after virus infection. The HLA class I ligandome was identified using high throughput mass spectrometry analyses, yielding 37 and 51 natural peptides processed and presented untreated and after acid stripping treatment VACV-infected human cells, respectively. Most of these virus ligands were identified in both conditions, but exclusive VACV ligands detected by mass spectrometry detected on acid stripping treatment doubled the number of those identified in the untreated VACV-infected condition. Theoretical binding affinity prediction of the VACV HLA-B*27:05 ligands and acute antiviral T cell response characterization in the HLA transgenic mice model showed no differences between HLA ligands identified under the two conditions: untreated and under acid stripping condition. These findings indicated that acid stripping treatment could be useful to identify HLA class I ligands from virus-infected cells.

scholarly journals HLA Class I Binding 9mer Peptides from Influenza A Virus Induce CD4+ T Cell Responses

PLoS ONE ◽  
2010 ◽  
Vol 5 (5) ◽  
pp. e10533 ◽  
Author(s):  
Mingjun Wang ◽  
Mette V. Larsen ◽  
Morten Nielsen ◽  
Mikkel Harndahl ◽  
Sune Justesen ◽  
...  
Keyword(s):  
T Cell ◽  
Influenza A Virus ◽  
Influenza A ◽  
T Cell Responses ◽  
Hla Class I ◽  
Cd4 T Cell ◽  
Class I ◽  
Cell Responses

scholarly journals Nucleophosmin leukaemic mutants contain C-terminus peptides that bind HLA class I molecules

Leukemia ◽  
2007 ◽  
Vol 22 (2) ◽  
pp. 424-426 ◽  
Author(s):  
A Liso ◽  
D Colau ◽  
R Benmaamar ◽  
A De Groot ◽  
W Martin ◽  
...  
Keyword(s):  
Hla Class I ◽  
Class I ◽  
Hla Class I Molecules ◽  
C Terminus

scholarly journals Variations in HLA-B cell surface expression, half-life and extracellular antigen receptivity

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Brogan Yarzabek ◽  
Anita J Zaitouna ◽  
Eli Olson ◽  
Gayathri N Silva ◽  
Jie Geng ◽  
...  
Keyword(s):  
Cell Surface ◽  
Half Life ◽  
Antigen Processing ◽  
Human Lymphocytes ◽  
Hla Class I ◽  
Surface Expression ◽  
Class I ◽  
Cell Surface Expression ◽  
Specific Expression ◽  
Hla Class I Molecules

The highly polymorphic human leukocyte antigen (HLA) class I molecules present peptide antigens to CD8+ T cells, inducing immunity against infections and cancers. Quality control mediated by peptide loading complex (PLC) components is expected to ensure the cell surface expression of stable peptide-HLA class I complexes. This is exemplified by HLA-B*08:01 in primary human lymphocytes, with both expression level and half-life at the high end of the measured HLA-B expression and stability hierarchies. Conversely, low expression on lymphocytes is measured for three HLA-B allotypes that bind peptides with proline at position 2, which are disfavored by the transporter associated with antigen processing. Surprisingly, these lymphocyte-specific expression and stability differences become reversed or altered in monocytes, which display larger intracellular pools of HLA class I than lymphocytes. Together, the findings indicate that allele and cell-dependent variations in antigen acquisition pathways influence HLA-B surface expression levels, half-lives and receptivity to exogenous antigens.

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