scholarly journals T-cell “induced-self” MHC class I/peptide complexes may enable “de novo” tolerance induction to neo-antigens occurring outside of the thymus

2017 ◽  
Vol 26 (6) ◽  
pp. 529-531 ◽  
Author(s):  
Thilo Oelert ◽  
Amos Gilhar ◽  
Ralf Paus
Keyword(s):  
T Cell ◽  
Mhc Class I ◽  
De Novo ◽  
Tolerance Induction ◽  
Class I ◽  
Peptide Complexes

Killed but Metabolically Active Recombinant Listeria monocytogenes as an Antigen Delivery and Activation Platform for Human Dendritic Cell-Based Cancer Immunotherapy.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3447-3447
Author(s):  
Dirk G. Brockstedt ◽  
Mojca Skoberne ◽  
Alice Yewdall ◽  
Keith S. Bahjat ◽  
Larry Corash ◽  
...  
Keyword(s):  
Listeria Monocytogenes ◽  
T Cell ◽  
Mhc Class I ◽  
Matrix Protein ◽  
Ex Vivo ◽  
Cd8 T Cell ◽  
Class I ◽  
Vaccine Platform ◽  
Maturation Stimulus ◽  
Peptide Complexes

Abstract Dendritic cells (DCs) are bone marrow-derived professional antigen presenting cells which play a pivotal role in initiating immune responses. To achieve optimal potency for priming of naive T cells, DCs must not only present high levels of MHC peptide complexes, but must also undergo maturation. An ideal DC-targeting vaccine formulation, therefore, should simultaneously deliver multiple antigens and activate DCs to increase expression of surface MHC-peptide complexes, costimulatory molecules, and production of immuno-stimulatory cytokines. Despite the development of a variety of ex vivo methods, no standard efficient and cost effective methods combining antigen loading and activation/maturation of DCs for clinical use currently exist. Here we report the development of a novel DC antigen-loading platform based on killed, but metabolically active (KBMA) recombinant Listeria monocytogenes (Lm). While recombinant Lm has a relatively long history as a cancer vaccine platform, its utility as a DC activation and loading platform has not been fully explored. KBMA Lm were 8-logs more sensitive to photochemical inactivation by the combined treatment of S-59 psoralen (amotosalen HCl) and long-wave ultraviolet light (S-59/UVA), by virtue of abrogation of nucleotide excision repair (NER) capacity, through engineered deletion of the bacterial UvrAB genes. Due to random distribution of infrequent psoralen adducts, KBMA Lm cannot propagate, but are metabolically active and can express their genetic repertoire, and program presentation of expressed heterologous antigens via the MHC class I and class II pathways. Infection of human monocyte-derived or blood myeloid DCs with KBMA Listeria induced their maturation and production of pro-inflammatory and pro- Th1 cytokines. The DCs achieved a fully mature phenotype, comparable to that induced by the standard maturation stimulus MCM-mimic. To determine whether KBMA Lm could program presentation of encoded antigens by the MHC class I pathway, we constructed a recombinant Lm vaccine expressing CD8+ T cell epitopes of influenza matrix protein (MP58–66) and MelanA/Mart-1 protein (Mart126–35). DCs infected with the recombinant KBMA Lm vaccine presented the recombinant class I epitopes and induced IFN-γ production by MP58–66- or Mart126–35-specific human CD8+ T cell clones. These studies demonstrate that KBMA Listeria is a novel and powerful ex vivo DC antigen loading platform combining a potent DC-maturation stimulus with the cytosolic delivery of recombinant antigen for presentation.

scholarly journals Homologies between SARS-CoV-2 and allergen proteins may direct T cell-mediated heterologous immune responses

2020 ◽  
Author(s):  
Kathrin Balz ◽  
Meng Chen ◽  
Abhinav Kaushik ◽  
Franz Cemic ◽  
Vanessa Heger ◽  
...  
Keyword(s):  
T Cell ◽  
Mhc Class I ◽  
Mhc Class Ii ◽  
De Novo ◽  
Class Ii ◽  
Cross Reactivity ◽  
Phleum Pratense ◽  
Class I ◽  
T Cell Epitopes ◽  
Allergen Sources

Abstract The outbreak of the new Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a public health emergency. Asthma does not represent a risk factor for COVID-19 in several published cohorts. We hypothesized that the SARS-CoV-2 proteome contains T cell epitopes, which are potentially cross-reactive to allergen epitopes. We aimed at identifying homologous peptide sequences by means of two distinct complementary bioinformatics approaches. Pipeline 1 included prediction of MHC Class I and Class II epitopes contained in the SARS-CoV-2 proteome and allergens along with alignment and elaborate ranking approaches. Pipeline 2 involved alignment of SARS-CoV-2 overlapping peptides with known allergen-derived T cell epitopes. Our results indicate a large number of MHC Class I epitope pairs including known as well as de novo predicted allergen T cell epitopes with high probability for cross-reactivity. Allergen sources, such as Aspergillus fumigatus, Phleum pratense and Dermatophagoides species are of particular interest due to their association with multiple cross-reactive candidate peptides, independently of the applied bioinformatic approach. In contrast, peptides derived from food allergens, as well as MHC class II epitopes did not achieve high in silico ranking and were therefore not further investigated. Our findings warrant further experimental confirmation along with examination of the functional importance of such cross-reactive responses.

scholarly journals Dimerization of soluble major histocompatibility complex-peptide complexes is sufficient for activation of T cell hybridoma and induction of unresponsiveness.

1995 ◽  
Vol 182 (2) ◽  
pp. 439-447 ◽  
Author(s):  
J P Abastado ◽  
Y C Lone ◽  
A Casrouge ◽  
G Boulot ◽  
P Kourilsky
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
Mhc Class I ◽  
Interleukin 2 ◽  
Surface Proteins ◽  
Class I ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Peptide Complexes ◽  
Mhc Class I Molecules

Major histocompatibility complex (MHC) class I molecules are cell-surface proteins that present peptides to CD8+ T cells. These peptides are mostly derived from endogenously synthesized protein. Recombinant, soluble MHC class I molecules were produced, purified, and loaded homogeneously with synthetic peptide. These MHC-peptide complexes were used to activate a T cell hybridoma. While monomers of MHC-peptide bound to the T cell, they showed no stimulatory activity. Dimers fully triggered the T cell hybridoma to secrete interleukin 2. This response was followed by a state in which the T cell was refractory to restimulation as a result of defective signal transduction through the T cell receptor.

T-cell-receptor-like antibodies – generation, function and applications

2012 ◽  
Vol 14 ◽  
Author(s):  
Rony Dahan ◽  
Yoram Reiter
Keyword(s):  
T Cell ◽  
Mhc Class I ◽  
T Cell Receptor ◽  
Cytotoxic T Cells ◽  
Membrane Surface ◽  
Cell Receptor ◽  
Class I ◽  
New Class ◽  
Infected Cells ◽  
Peptide Complexes

Tumour and virus-infected cells are recognised by CD8+ cytotoxic T cells that, in response, are activated to eliminate these cells. In order to be activated, the clonotypic T-cell receptor (TCR) needs to encounter a specific peptide antigen presented by the membrane surface major histocompatibility complex (MHC) molecule. Cells that have undergone malignant transformation or viral infection present peptides derived from tumour-associated antigens or viral proteins on their MHC class I molecules. Therefore, disease-specific MHC–peptide complexes are desirable targets for immunotherapeutic approaches. One such approach transforms the unique fine specificity but low intrinsic affinity of TCRs to MHC–peptide complexes into high-affinity soluble antibody molecules endowed with a TCR-like specificity towards tumour or viral epitopes. These antibodies, termed TCR-like antibodies, are being developed as a new class of immunotherapeutics that can target tumour and virus-infected cells and mediate their specific killing. In addition to their therapeutic capabilities, TCR-like antibodies are being developed as diagnostic reagents for cancer and infectious diseases, and serve as valuable research tools for studying MHC class I antigen presentation.

scholarly journals Homologies between SARS-CoV-2 and allergen proteins may direct T cell-mediated heterologous immune responses

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kathrin Balz ◽  
Abhinav Kaushik ◽  
Meng Chen ◽  
Franz Cemic ◽  
Vanessa Heger ◽  
...  
Keyword(s):  
T Cell ◽  
Mhc Class I ◽  
Mhc Class Ii ◽  
De Novo ◽  
Class Ii ◽  
Cross Reactivity ◽  
Phleum Pratense ◽  
Class I ◽  
T Cell Epitopes ◽  
Allergen Sources

AbstractThe outbreak of the new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a public health emergency. Asthma does not represent a risk factor for COVID-19 in several published cohorts. We hypothesized that the SARS-CoV-2 proteome contains T cell epitopes, which are potentially cross-reactive to allergen epitopes. We aimed at identifying homologous peptide sequences by means of two distinct complementary bioinformatics approaches. Pipeline 1 included prediction of MHC Class I and Class II epitopes contained in the SARS-CoV-2 proteome and allergens along with alignment and elaborate ranking approaches. Pipeline 2 involved alignment of SARS-CoV-2 overlapping peptides with known allergen-derived T cell epitopes. Our results indicate a large number of MHC Class I epitope pairs including known as well as de novo predicted allergen T cell epitopes with high probability for cross-reactivity. Allergen sources, such as Aspergillus fumigatus, Phleum pratense and Dermatophagoides species are of particular interest due to their association with multiple cross-reactive candidate peptides, independently of the applied bioinformatic approach. In contrast, peptides derived from food allergens, as well as MHC class II epitopes did not achieve high in silico ranking and were therefore not further investigated. Our findings warrant further experimental confirmation along with examination of the functional importance of such cross-reactive responses.

Identification of tumor-associated MHC class I ligands by a novel T cell-independent approach

2000 ◽  
Vol 30 (18) ◽  
pp. 2216 ◽  
Author(s):  
Markus Schirle ◽  
Wieland Keilholz ◽  
Bernd Weber ◽  
Cécile Gouttefangeas ◽  
Tilman Dumrese ◽  
...  
Keyword(s):  
T Cell ◽  
Mhc Class I ◽  
Class I
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