scholarly journals Different Endosomal Proteolysis Requirements for Antigen Processing of Two T-cell Epitopes of the M5 Protein from ViableStreptococcus pyogenes

1998 ◽  
Vol 273 (6) ◽  
pp. 3291-3295 ◽  
Author(s):  
Alexei A. Delvig ◽  
John H. Robinson
Keyword(s):  
T Cell ◽  
Antigen Processing ◽  
T Cell Epitopes

scholarly journals Endogenous Presentation of CD8+ T Cell Epitopes from Epstein-Barr Virus–encoded Nuclear Antigen 1

2004 ◽  
Vol 199 (10) ◽  
pp. 1421-1431 ◽  
Author(s):  
Judy Tellam ◽  
Geoff Connolly ◽  
Katherine J. Green ◽  
John J. Miles ◽  
Denis J. Moss ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
Antigen Processing ◽  
Epstein Barr Virus ◽  
Cd8 T Cell ◽  
Nuclear Antigen ◽  
T Cell Epitopes ◽  
Barr Virus ◽  
Degradation Rates ◽  
Epstein Barr

Epstein-Barr virus (EBV)–encoded nuclear antigen (EBNA)1 is thought to escape cytotoxic T lymphocyte (CTL) recognition through either self-inhibition of synthesis or by blockade of proteasomal degradation by the glycine-alanine repeat (GAr) domain. Here we show that EBNA1 has a remarkably varied cell type–dependent stability. However, these different degradation rates do not correspond to the level of major histocompatibility complex class I–restricted presentation of EBNA1 epitopes. In spite of the highly stable expression of EBNA1 in B cells, CTL epitopes derived from this protein are efficiently processed and presented to CD8+ T cells. Furthermore, we show that EBV-infected B cells can readily activate EBNA1-specific memory T cell responses from healthy virus carriers. Functional assays revealed that processing of these EBNA1 epitopes is proteasome and transporter associated with antigen processing dependent. We also show that the endogenous presentation of these epitopes is dependent on the newly synthesized protein rather than the long-lived stable EBNA1. Based on these observations, we propose that defective ribosomal products, not the full-length antigen, are the primary source of endogenously processed CD8+ T cell epitopes from EBNA1.

scholarly journals Suppressive effect of antibody on processing of T cell epitopes.

1993 ◽  
Vol 178 (4) ◽  
pp. 1459-1463 ◽  
Author(s):  
C Watts ◽  
A Lanzavecchia
Keyword(s):  
T Cell ◽  
Antigen Processing ◽  
Suppressive Effect ◽  
T Cell Epitopes ◽  
Strong Suppression ◽  
Lysosomal Ph ◽  
Mhc Molecules ◽  
Class Ii Mhc ◽  
Formed Part ◽  
Antigen Presenting

Immunoglobulins drive efficient antigen capture by antigen presenting cells for processing and presentation on class II MHC-molecules. High affinity antibody/antigen interactions are stable at endosomal/lysosomal pH thus altering the substrate for antigen processing. We show that this can result in strong suppression of presentation of some T cell epitopes. This effect was observed when the antibody specificity was a B cell surface Ig, or formed part of an immune complex. In the latter case the presence of the suppressing antibody boosts presentation of other T cell epitopes through enhanced uptake into Fc receptor bearing cells. The influence of bound antibodies on the outcome of antigen processing may influence with T cell epitopes dominate T cell responses and may change the focus of the response with time.

scholarly journals Glycan-regulated Antigen Processing of a Protein in the Endoplasmic Reticulum Can Uncover Cryptic Cytotoxic T Cell Epitopes

1998 ◽  
Vol 188 (4) ◽  
pp. 773-778 ◽  
Author(s):  
Philip Wood ◽  
Tim Elliott
Keyword(s):  
Endoplasmic Reticulum ◽  
T Cell ◽  
T Lymphocyte ◽  
Influenza A ◽  
Antigen Processing ◽  
Secretory Pathway ◽  
Cytotoxic T Lymphocyte ◽  
Cytotoxic T Cell ◽  
T Cell Epitopes ◽  
Ctl Epitopes

We and others have shown that influenza A nucleoprotein (NP) targeted to the secretory pathway cannot be processed to yield several cytotoxic T lymphocyte (CTL) epitopes in cell lines that lack the transporter associated with antigen processing (TAP). However, a large COOH-terminal fragment of NP is processed and presented in these cells. Full-length NP is cotranslationally glycosylated in the lumen of the endoplasmic reticulum at two sites distal to the major H2-Kk and H2-Db restricted CTL epitopes, and we show here that pharmacological or genetic inhibition of N-linked glycosylation, leads to the processing and presentation of both these epitopes in a TAP-independent way.

scholarly journals Induction of Tolerance to Therapeutic Proteins With Antigen-Processing Independent T Cell Epitopes: Controlling Immune Responses to Biologics

2021 ◽  
Vol 12 ◽  
Author(s):  
Evelien Schurgers ◽  
David C. Wraith
Keyword(s):  
T Cell ◽  
Antigen Processing ◽  
Tolerance Induction ◽  
Gene Replacement ◽  
Immunological Tolerance ◽  
Clotting Factor ◽  
T Cell Epitopes ◽  
Enzyme Replacement ◽  
Therapeutic Benefits ◽  
Recombinant Fviii

The immune response to exogenous proteins can overcome the therapeutic benefits of immunotherapies and hamper the treatment of protein replacement therapies. One clear example of this is haemophilia A resulting from deleterious mutations in the FVIII gene. Replacement with serum derived or recombinant FVIII protein can cause anti-drug antibodies in 20-50% of individuals treated. The resulting inhibitor antibodies override the benefit of treatment and, at best, make life unpredictable for those treated. The only way to overcome the inhibitor issue is to reinstate immunological tolerance to the administered protein. Here we compare the various approaches that have been tested and focus on the use of antigen-processing independent T cell epitopes (apitopes) for tolerance induction. Apitopes are readily designed from any protein whether this is derived from a clotting factor, enzyme replacement therapy, gene therapy or therapeutic antibody.

scholarly journals Antigen processing by nardilysin and thimet oligopeptidase generates cytotoxic T cell epitopes

2010 ◽  
Vol 12 (1) ◽  
pp. 45-53 ◽  
Author(s):  
Jan H Kessler ◽  
Selina Khan ◽  
Ulrike Seifert ◽  
Sylvie Le Gall ◽  
K Martin Chow ◽  
...  
Keyword(s):  
T Cell ◽  
Antigen Processing ◽  
Cytotoxic T Cell ◽  
T Cell Epitopes ◽  
Thimet Oligopeptidase

scholarly journals Link between Organ-specific Antigen Processing by 20S Proteasomes and CD8+ T Cell–mediated Autoimmunity

2002 ◽  
Vol 195 (8) ◽  
pp. 983-990 ◽  
Author(s):  
Ulrike Kuckelkorn ◽  
Thomas Ruppert ◽  
Britta Strehl ◽  
Peter R. Jungblut ◽  
Ursula Zimny-Arndt ◽  
...  
Keyword(s):  
T Cells ◽  
Small Intestine ◽  
T Cell ◽  
Cd8 T Cells ◽  
Antigen Processing ◽  
Specific Antigen ◽  
Cd8 T Cell ◽  
T Cell Epitopes ◽  
Tissue Specific ◽  
Organ Specific

Adoptive transfer of cross-reactive HSP60-specific CD8+ T cells into immunodeficient mice causes autoimmune intestinal pathology restricted to the small intestine. We wondered whether local immunopathology induced by CD8+ T cells can be explained by tissue-specific differences in proteasome-mediated processing of major histocompatibility complex class I T cell epitopes. Our experiments demonstrate that 20S proteasomes of different organs display a characteristic composition of α and β chain subunits and produce distinct peptide fragments with respect to both quality and quantity. Digests of HSP60 polypeptides by 20S proteasomes show most efficient generation of the pathology related CD8+ T cell epitope in the small intestine. Further, we demonstrate that the organ-specific potential to produce defined T cell epitopes reflects quantities that are relevant for cytotoxic T lymphocyte recognition. We propose tissue-specific antigen processing by 20S proteasomes as a potential mechanism to control organ-specific immune responses.

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