Genetic Restriction of Responses to Peptide Antigens

Vaccines ◽  
1995 ◽  
pp. 141-146
Author(s):  
M. J. Francis
Keyword(s):  
Peptide Antigens ◽  
Genetic Restriction

scholarly journals Serological Responses to Toxoplasma gondii and Matrix Antigen 1 Predict the Risk of Subsequent Toxoplasmic Encephalitis in People Living with HIV

2021 ◽  
Author(s):  
Jianchun Xiao ◽  
Fiona Bhondoekhan ◽  
Eric C Seaberg ◽  
Otto Yang ◽  
Valentina Stosor ◽  
...  
Keyword(s):  
Predictive Performance ◽  
Toxoplasmic Encephalitis ◽  
People Living With Hiv ◽  
Serum Samples ◽  
Peptide Antigens ◽  
Unit Increase ◽  
At Risk Populations ◽  
Living With Hiv ◽  
Nested Case Control ◽  
Control Study

Abstract Background Clinically useful predictors for fatal toxoplasmosis are lacking. We investigated the value of serological assays for antibodies to whole Toxoplasma antigens and to peptide antigens of the Toxoplasma cyst protein MAG1, for predicting incident toxoplasmic encephalitis (TE) in people living with HIV (PLWH). Methods We performed a nested case control study, conducted within the Multicenter AIDS Cohort Study (MACS), using serum samples obtained 2 years prior to diagnosis of TE from 28 cases, and 37 HIV disease-matched Toxoplasma seropositive controls at matched time-points. Sera were tested for Toxoplasma antibodies using a commercial assay and for antibodies to MAG1_4.2 and MAG1_5.2 peptides in ELISA. Results Two years prior to clinical diagnosis, 68% of TE cases were MAG1_4.2 seropositive compared with 16% of controls (OR 25.0, 95% CI 3.14-199.18). Corresponding results for MAG1_5.2 seropositivity were 36% and 14% (OR 3.6, 95% CI 0.95-13.42). Higher levels of antibody to MAG1_4.2 (OR 18.5 per doubling of the OD value, 95% CI 1.41-242) and to Toxoplasma (OR 2.91 for each OD unit increase, 95% CI 1.48-5.72) were also associated with the risk of TE. When seropositivity was defined as the presence of MAG1 antibody or relatively high levels of Toxoplasma antibody, the sensitivity was 89% and specificity was 68% for subsequent TE. Conclusions Antibodies to MAG1 showed predictive value on the occurrence of TE in PLWH, and the predictive performance was further improved by adding the levels of Toxoplasma antibody. These measures could be clinically useful for predicting subsequent diseases in multiple at-risk populations.

scholarly journals Multiplex serological assay for establishing serological profiles of polymorphic, closely related peptide antigens

MethodsX ◽  
2021 ◽  
pp. 101345
Author(s):  
Jessica Bolton ◽  
Sidhartha Chaudhury ◽  
Randall S. MacGill ◽  
Angela M. Early ◽  
C. Richter King ◽  
...  
Keyword(s):  
Serological Assay ◽  
Peptide Antigens ◽  
Related Peptide

scholarly journals ELISA based on peptide antigens reproducing cross-reactive viral epitopes to detect antibodies in Latent Autoimmune Diabetes in Adults vs. Type 1 Diabetes

MethodsX ◽  
2021 ◽  
pp. 101452
Author(s):  
Feliciana Real-Fernández ◽  
Alessandra Gallo ◽  
Francesca Nuti ◽  
Lorenzo Altamore ◽  
Gloria Giovanna Del Vescovo ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Autoimmune Diabetes ◽  
Peptide Antigens ◽  
Latent Autoimmune Diabetes

Influence of Conjugation Chemistry and B Epitope Orientation on the Immune Response of Branched Peptide Antigens

2013 ◽  
Vol 24 (4) ◽  
pp. 578-585 ◽  
Author(s):  
M. Monsó ◽  
B. G. de la Torre ◽  
E. Blanco ◽  
N. Moreno ◽  
D. Andreu
Keyword(s):  
Immune Response ◽  
Peptide Antigens ◽  
Conjugation Chemistry

scholarly journals Modulation of Antigen Display on PapMV Nanoparticles Influences Its Immunogenicity

Vaccines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 33
Author(s):  
Marie-Eve Laliberté-Gagné ◽  
Marilène Bolduc ◽  
Caroline Garneau ◽  
Santa-Mariela Olivera-Ugarte ◽  
Pierre Savard ◽  
...  
Keyword(s):  
Immune Response ◽  
Influenza A ◽  
Matrix Protein ◽  
Cell Epitope ◽  
Vaccine Antigen ◽  
Vaccine Platform ◽  
Peptide Antigens ◽  
C Terminus ◽  
The Impact ◽  
Stimulation Of

Background: The papaya mosaic virus (PapMV) vaccine platform is a rod-shaped nanoparticle made of the recombinant PapMV coat protein (CP) self-assembled around a noncoding single-stranded RNA (ssRNA) template. The PapMV nanoparticle induces innate immunity through stimulation of the Toll-like receptors (TLR) 7 and 8. The display of the vaccine antigen at the surface of the nanoparticle, associated with the co-stimulation signal via TLR7/8, ensures a strong stimulation of the immune response, which is ideal for the development of candidate vaccines. In this study, we assess the impact of where the peptide antigen is fused, whether at the surface or at the extremities of the nanoparticles, on the immune response directed to that antigen. Methods: Two different peptides from influenza A virus were used as model antigens. The conserved M2e peptide, derived from the matrix protein 2 was chosen as the B-cell epitope, and a peptide derived from the nucleocapsid was chosen as the cytotoxic T lymphocytes (CTL) epitope. These peptides were coupled at two different positions on the PapMV CP, the N- (PapMV-N) or the C-terminus (PapMV-C), using the transpeptidase activity of Sortase A (SrtA). The immune responses, both humoral and CD8+ T-cell-mediated, directed to the peptide antigens in the two different fusion contexts were analyzed and compared. The impact of coupling density at the surface of the nanoparticle was also investigated. Conclusions: The results demonstrate that coupling of the peptide antigens at the N-terminus (PapMV-N) of the PapMV CP led to an enhanced immune response to the coupled peptide antigens as compared to coupling to the C-terminus. The difference between the two vaccine platforms is linked to the enhanced capacity of the PapMV-N vaccine platform to stimulate TLR7/8. We also demonstrated that the strength of the immune response increases with the density of coupling at the surface of the nanoparticles.

scholarly journals An HLA-A2-restricted tyrosinase antigen on melanoma cells results from posttranslational modification and suggests a novel pathway for processing of membrane proteins.

1996 ◽  
Vol 183 (2) ◽  
pp. 527-534 ◽  
Author(s):  
J C Skipper ◽  
R C Hendrickson ◽  
P H Gulden ◽  
V Brichard ◽  
A Van Pel ◽  
...  
Keyword(s):  
Posttranslational Modification ◽  
Melanoma Cells ◽  
Amino Acid Sequences ◽  
Class I ◽  
Antigenic Peptides ◽  
Peptide Antigens ◽  
Mhc Molecules ◽  
Tyrosinase Gene ◽  
Histocompatibility Complex ◽  
Natural Peptide

T lymphocytes recognize antigens consisting of peptides presented by class I and II major histocompatibility complex (MHC) molecules. The peptides identified so far have been predictable from the amino acid sequences of proteins. We have identified the natural peptide target of a CTL clone that recognizes the tyrosinase gene product on melanoma cells. The peptide results from posttranslational conversion of asparagine to aspartic acid. This change is of central importance for peptide recognition by melanoma-specific T cells, but has no impact on peptide binding to the MHC molecule. This posttranslational modification has not been previously described for any MHC-associated peptide and represents the first demonstration of posttranslational modification of a naturally processed class I-associated peptide. This observation is relevant to the identification and prediction of potential peptide antigens. The most likely mechanism for production of this peptide leads to the suggestion that antigenic peptides can be derived from proteins that are translated into the endoplasmic reticulum.

scholarly journals Enhancing and inhibitory motifs have coevolved to regulate CD4 activity

2021 ◽  
Author(s):  
Mark S. Lee ◽  
Peter J. Tuohy ◽  
Caleb Kim ◽  
Katrina Lichauco ◽  
Heather L. Parrish ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Purifying Selection ◽  
Cell Receptor ◽  
Specific Information ◽  
Transmembrane Receptors ◽  
Peptide Antigens ◽  
And Function ◽  
Intracellular Domains

SUMMARYCD4+ T cells use T cell receptor (TCR)-CD3 complexes, and CD4, to respond to peptide antigens within MHCII molecules (pMHCII). We report here that, through ∼435 million years of evolution in jawed vertebrates, purifying selection has shaped motifs in the extracellular, transmembrane, and intracellular domains of eutherian CD4 that both enhance pMHCII responses and are coevolving with residues in an intracellular motif that inhibits pMHCII responses. Importantly, while CD4 interactions with the Src kinase, Lck, are classically viewed as the key determinant of CD4’s contribution to pMHCII responses, we found that without the inhibitory motif CD4-Lck interactions are not necessary for robust responses to pMHCII. In summary, motifs that mediate events on the outside and inside of CD4+ T cells coevolved to finetune the relay of pMHCII-specific information across the membrane. These results have implications for the evolution and function of complex transmembrane receptors and for biomimetic engineering.

scholarly journals CD8 coreceptor-mediated focusing can reorder the agonist hierarchy of peptide ligands recognized via the T cell receptor

2020 ◽  
Author(s):  
Mathew Clement ◽  
Lea Knezevic ◽  
Tamsin Dockree ◽  
James E. McLaren ◽  
Kristin Ladell ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Theoretical Models ◽  
Cell Receptor ◽  
Dissociation Rate ◽  
Peptide Ligands ◽  
Controlled System ◽  
Peptide Antigens ◽  
Histocompatibility Complex ◽  
The Relationship

ABSTRACTCD8+ T cells are inherently cross-reactive and recognize numerous peptide antigens in the context of a given major histocompatibility complex class I (MHCI) molecule via the clonotypically expressed T cell receptor (TCR). The lineally expressed coreceptor CD8 interacts coordinately with MHCI at a distinct and largely invariant site to slow the TCR/peptide-MHCI (pMHCI) dissociation rate and enhance antigen sensitivity. However, this biological effect is not necessarily uniform, and theoretical models suggest that antigen sensitivity can be modulated in a differential manner by CD8. We used an intrinsically controlled system to determine how the relationship between the TCR/pMHCI interaction and the pMHCI/CD8 interaction affects the functional sensitivity of antigen recognition. Our data show that modulation of the pMHCI/CD8 interaction can reorder the agonist hierarchy of peptide ligands across a spectrum of affinities for the TCR.SIGNIFICANCESufficient immune coverage of the peptide universe within a finite host requires highly degenerate T cell receptors (TCRs). However, this inherent need for antigen cross-recognition is associated with a high risk of autoimmunity, which can only be mitigated by a process of adaptable specificity. We describe a mechanism that resolves this conundrum by allowing individual clonotypes to focus on specific peptide ligands without alterations to the structure of the TCR.

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