Immunogenicity of Self Antigens is Unrelated to MHC-binding Affinity: T-cell Determinant Structure of Golli-MBP in the BALB/c Mouse

2000 ◽  
Vol 15 (3) ◽  
pp. 315-322 ◽  
Author(s):  
Emanual Maverakis ◽  
Richard Mendoza ◽  
Scott Southwood ◽  
Claudia Raja-Gabaglia ◽  
Sara Abromson-Leeman ◽  
...  
Keyword(s):  
T Cell ◽  
Binding Affinity ◽  
Determinant Structure ◽  
Self Antigens

Prediction of Prophylactic Peptide Vaccine Candidates for Human Papillomavirus (HPV): An Immunoinformatics and Reverse Vaccinology Approach

2020 ◽  
Vol 17 ◽  
Author(s):  
Mehreen Ismail ◽  
Zureesha Sajid ◽  
Amjad Ali ◽  
Xiaogang Wu ◽  
Syed Aun Muhammad ◽  
...  
Keyword(s):  
T Cells ◽  
Human Papillomavirus ◽  
T Cell ◽  
Binding Affinity ◽  
Cd8 T Cells ◽  
Reverse Vaccinology ◽  
Host Immune System ◽  
T Cell Epitopes ◽  
Multiple Alleles ◽  
Vaccine Candidates

Background: Human Papillomavirus (HPV) is responsible for substantial morbidity and mortality worldwide. We predicted immunogenic promiscuous monovalent and polyvalent T-cell epitopes from the polyprotein of the Human Papillomavirus (HPV) using a range of bioinformatics tools and servers. Methods: We used immunoinformatics and reverse vaccinology-based approaches to design prophylactic peptides by antigenicity analysis, Tcell epitopes prediction, proteasomal and conservancy evaluation, host-pathogen protein interactions, and in silico binding affinity analysis. Results: We found two early proteins (E2 and E6) and two late proteins (L1 and L2) of HPV as potential vaccine candidates. Of these proteins (E2, E6, L1 & L2), 2-epitopes of each candidate protein for multiple alleles of MHC class I and II bearing significant binding affinity (>-6.0 kcal/mole). These potential epitopes for CD4+ and CD8+ T-cells were also linked to design polyvalent construct using GPGPG linkers. Cholera toxin B and mycobacterial heparin-binding hemagglutinin adjuvant with a molecular weight of 12.5 and 18.5 kDa were used for epitopes of CD4+ and CD8+ T-cells respectively. The molecular docking indicated the optimum binding affinity of HPV peptides with MHC molecules. This interaction showed that our predicted vaccine candidates are suitable to trigger the host immune system to prevent HPV infections. Conclusion: The predicted conserved T-cell epitopes would contribute to the imminent design of HPV vaccine candidates, which will be able to induce a broad range of immune-responses in a heterogeneous HLA population.

Immune Responses to Retinal Self-Antigens in CD25+CD4+Regulatory T-Cell–Depleted Mice

2004 ◽  
Vol 45 (6) ◽  
pp. 1879 ◽  
Author(s):  
Masaru Takeuchi ◽  
Hiroshi Keino ◽  
Takeshi Kezuka ◽  
Masahiko Usui ◽  
Osamu Taguchi
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Regulatory T Cell ◽  
Self Antigens

scholarly journals The Thymic Repertoire of Neuroendocrine-Related Self Antigens: Biological Role in T-Cell Selection and Pharmacological Implications

1999 ◽  
Vol 6 (1-2) ◽  
pp. 115-125 ◽  
Author(s):  
Vincent Geenen ◽  
Ouafae Kecha ◽  
Fabienne Brilot ◽  
Chantal Charlet-Renard ◽  
Henri Martens
Keyword(s):  
T Cell ◽  
Biological Role ◽  
Cell Selection ◽  
T Cell Selection ◽  
Self Antigens

scholarly journals Langerhans Cells Are Not Required for the CD8 T Cell Response to Epidermal Self-Antigens

2009 ◽  
Vol 182 (8) ◽  
pp. 4657-4664 ◽  
Author(s):  
Laura S. Bursch ◽  
Benjamin E. Rich ◽  
Kristin A. Hogquist
Keyword(s):  
T Cell ◽  
Cell Response ◽  
Langerhans Cells ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Self Antigens

T-cell tolerance and autoimmunity to systemic and tissue-restricted self-antigens

2005 ◽  
Vol 204 (1) ◽  
pp. 116-127 ◽  
Author(s):  
Jens Lohr ◽  
Birgit Knoechel ◽  
Vijaya Nagabhushanam ◽  
Abul K. Abbas
Keyword(s):  
T Cell ◽  
T Cell Tolerance ◽  
Cell Tolerance ◽  
Self Antigens

scholarly journals A Superantigen-Antibody Fusion Protein for T-Cell Immunotherapy of Human B-Lineage Malignancies

Blood ◽  
1997 ◽  
Vol 89 (6) ◽  
pp. 2089-2097 ◽  
Author(s):  
Cecilia Gidlöf ◽  
Mikael Dohlsten ◽  
Peter Lando ◽  
Terje Kalland ◽  
Christer Sundström ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Fusion Protein ◽  
B Cell ◽  
Binding Affinity ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Target Cells ◽  
Cell Based Therapy ◽  
B Lineage

Abstract The bacterial superantigen staphylococcal enterotoxin A (SEA) is an efficient activator of cytotoxic T cells when presented on major histocompatibility complex (MHC) class II molecules of target cells. Our previous studies showed that such SEA-directed T cells efficiently lysed chronic B-lymphocytic leukemia (B-CLL) cells. Next, we made a mutated SEA–protein A (SEAm-PA) fusion protein with more than 1,000-fold reduced binding affinity for MHC class II compared with native SEA. The fusion protein was successfully used to direct T cells to B-CLL cells coated with different B lineage–directed monoclonal antibodies (MoAbs). In this communication, we constructed a recombinant anti-CD19-Fab-SEAm fusion protein. The MHC class II binding capacity of the SEA part was drastically reduced by a D227A point mutation, whereas the T-cell activation properties were retained. The Fab part of the fusion protein displayed a binding affinity for CD19+ cells in the nanomolar range. The anti-CD19-Fab-SEAm molecule mediated effective, specific, rapid, and perforin-like T-cell lysis of B-CLL cells at low effector to target cell ratios. Normal CD19+ B cells were sensitive to lysis, whereas CD34+ progenitor cells and monocytes/macrophages were resistant. A panel of CD19+ B-cell lines representing different B-cell developmental stages were efficiently lysed, and the sensitivity correlated with surface ICAM-1 expression. The anti-CD19-Fab-SEAm fusion protein mediated highly effective killing of tumor biopsy cells representing several types of B-cell non-Hodgkin's lymphoma (B-NHL). Humanized severe combined immune deficiency (SCID) mice carrying Daudi lymphoma cells were used as an in vivo therapy model for evaluation of the anti-CD19-Fab-SEAm fusion protein. Greater than 90% reduction in tumor weight was recorded in anti-CD19-Fab-SEAm–treated animals compared with control animals receiving an irrelevant Fab-SEAm fusion protein. The present results indicate that MoAb-targeted superantigens (SAgs) may represent a promising approach for T-cell–based therapy of CD19+ B-cell malignancies.

scholarly journals Robust Iterative Stimulation with Self-Antigens Overcomes CD8+ T Cell Tolerance to Self- and Tumor Antigens

Cell Reports ◽  
2019 ◽  
Vol 28 (12) ◽  
pp. 3092-3104.e5 ◽  
Author(s):  
Christine E. Nelson ◽  
Emily A. Thompson ◽  
Clare F. Quarnstrom ◽  
Kathryn A. Fraser ◽  
Davis M. Seelig ◽  
...  
Keyword(s):  
T Cell ◽  
Tumor Antigens ◽  
Cd8 T Cell ◽  
T Cell Tolerance ◽  
Cell Tolerance ◽  
Self Antigens

scholarly journals CD8 T cell autoreactivity to preproinsulin epitopes with very low human leucocyte antigen class I binding affinity

2012 ◽  
Vol 170 (1) ◽  
pp. 57-65 ◽  
Author(s):  
J. R. F. Abreu ◽  
S. Martina ◽  
A. A. Verrijn Stuart ◽  
Y. E. Fillié ◽  
K. L. M. C. Franken ◽  
...  
Keyword(s):  
T Cell ◽  
Binding Affinity ◽  
Human Leucocyte Antigen ◽  
Cd8 T Cell ◽  
Class I ◽  
Human Leucocyte Antigen Class
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