scholarly journals Route of Antigen Presentation Can Determine the Selection of Foxp3-Dependent or Foxp3-Independent Dominant Immune Tolerance

2017 ◽  
Vol 200 (1) ◽  
pp. 101-109 ◽  
Author(s):  
Ana Agua-Doce ◽  
Marta Caridade ◽  
Vanessa G. Oliveira ◽  
Lisa Bergman ◽  
Maria C. Lafaille ◽  
...  
2019 ◽  
pp. 2-20
Author(s):  
Bibiana Bielekova

The chapter begins with a short introduction to the components of the immune system, outlining both the innate and adaptive components. It discusses the role of the immune system in protecting against infections and abnormal tissues. It describes the concepts of self-antigens, antigen presentation, and immune synapse. It then examines immune tolerance and the differing functions and capacities of the innate and adaptive immune systems. Finally, the chapter considers infections and autoimmune phenomena and how the immune system responds to these challenges.


1996 ◽  
Vol 184 (4) ◽  
pp. 1579-1584 ◽  
Author(s):  
S Joyce ◽  
I Negishi ◽  
A Boesteanu ◽  
A D DeSilva ◽  
P Sharma ◽  
...  

Thymic selection of natural killer-1+ natural T cells that express alpha beta T cell receptors requires a conserved beta 2-microglobulin-associated molecule, presumably CD1d, displayed by CD4+8+ thymocytes. Here we demonstrate that positive selection of natural T cells occurs independent of transporters associated with antigen presentation-1 (TAP-1) function. Moreover, natural T cells in TAP-1o/o mice are numerically expanded. Several H-2 class Ib molecules function in a TAP-independent manner, suggesting that if expressed in TAP-1o/o thymocytes, they could play a role in natural T cell development. Of these class Ib molecules, H-2TL is expressed by TAP-1o/o thymocytes. Moreover, we find that thymi of TL+ mice congenic or transgenic for H-2T18 also have a numerically expanded natural T cell repertoire compared with TL- mice. This expansion, as in TAP-1o/o thymi, is evident in each of the limited T cell receptor V beta chains expressed by natural T cells, suggesting that TL and CD1d impact similar repertoires. Thus TL, in addition to CD1d, plays a role in natural T cell development.


2019 ◽  
Author(s):  
Radhika R. Gudi ◽  
Subha Karumuthil-Melethil ◽  
Nicolas Perez ◽  
Gongbo Li ◽  
Chenthamarakshan Vasu

AbstractInhibitory/repressor-receptors are upregulated significantly on activated T cells, and have been the molecules of attention as targets for inducing immune tolerance. Induction of effective antigen specific tolerance depends on concurrent engagement of the TCR and one or more of these inhibitory receptors. Here, we show, for the first time that dendritic cells (DCs) can be efficiently engineered to express multiple T cell inhibitory ligands, and enhanced engagement of T cell inhibitory receptors, upon antigen presentation, by these DCs can induce effective CD4+ T cell tolerance and suppress autoimmunity. Compared to control DCs, antigen presentation by DCs that ectopically express CTLA4, PD1 and BTLA selective ligands (B7.1wa, PD-L1, and HVEM-CRD1 respectively) individually (mono-ligand DCs) or in combination (multi-ligand DCs) causes an inhibition of CD4+ T cell proliferation and pro-inflammatory cytokine response, as well as increase in Foxp3+ Treg frequency and immune regulatory cytokine production. Administration of self-antigen (mouse thyroglobulin; mTg) loaded multi-ligand DCs caused hyporesponsiveness to mTg challenge, suppression of autoantibody production, and amelioration of experimental autoimmune thyroiditis. Overall, this study shows that engineered DC-directed enhanced concurrent activation of multiple T cell coinhibitory pathways is an effective way to induce self-antigen specific T cell tolerance to suppress ongoing autoimmunity.


Immunity ◽  
2013 ◽  
Vol 39 (6) ◽  
pp. 1070-1081 ◽  
Author(s):  
Muhammad Baghdadi ◽  
Akihiro Yoneda ◽  
Tsunaki Yamashina ◽  
Hiroko Nagao ◽  
Yoshihiro Komohara ◽  
...  

2021 ◽  
pp. ji1901301
Author(s):  
Meng Li ◽  
Arata Itoh ◽  
Jingchao Xi ◽  
Chunsong Yu ◽  
Yuehong Wu ◽  
...  

2020 ◽  
Author(s):  
Antonius A. de Waard ◽  
Tamara Verkerk ◽  
Kelly Hoefakker ◽  
Dirk M. van der Steen ◽  
Marlieke L.M. Jongsma ◽  
...  

AbstractTumors with an impaired transporter associated with antigen processing (TAP) present several ER-derived self-antigens on HLA class I (HLA-I) which are absent on healthy cells. Selection of such TAP-independent antigens for T cell-based immunotherapy should include analysis of their expression on healthy cells to prevent therapy-induced adverse toxicities. However, it is unknown how the absence of clinically relevant antigens on healthy cells needs to be validated. Here we monitored TAP-independent antigen presentation on various healthy cells using a new toolbox consisting of a T cell clone recognizing a TAP-independent SSR1-derived antigen. We found that most but not all healthy cells present this antigen under normal and inflammatory conditions, indicating that TAP-independent antigen presentation is a variable phenomenon. Our data emphasize the necessity of extensive testing of a wide variety of healthy cell types to define clinically relevant TAP-independent antigens that can be safely targeted by immunotherapy.


2011 ◽  
Vol 187 (11) ◽  
pp. 5921-5930 ◽  
Author(s):  
Aaron W. Michels ◽  
David A. Ostrov ◽  
Li Zhang ◽  
Maki Nakayama ◽  
Masanori Fuse ◽  
...  

2019 ◽  
Vol 42 ◽  
Author(s):  
Gian Domenico Iannetti ◽  
Giorgio Vallortigara

Abstract Some of the foundations of Heyes’ radical reasoning seem to be based on a fractional selection of available evidence. Using an ethological perspective, we argue against Heyes’ rapid dismissal of innate cognitive instincts. Heyes’ use of fMRI studies of literacy to claim that culture assembles pieces of mental technology seems an example of incorrect reverse inferences and overlap theories pervasive in cognitive neuroscience.


1975 ◽  
Vol 26 ◽  
pp. 395-407
Author(s):  
S. Henriksen

The first question to be answered, in seeking coordinate systems for geodynamics, is: what is geodynamics? The answer is, of course, that geodynamics is that part of geophysics which is concerned with movements of the Earth, as opposed to geostatics which is the physics of the stationary Earth. But as far as we know, there is no stationary Earth – epur sic monere. So geodynamics is actually coextensive with geophysics, and coordinate systems suitable for the one should be suitable for the other. At the present time, there are not many coordinate systems, if any, that can be identified with a static Earth. Certainly the only coordinate of aeronomic (atmospheric) interest is the height, and this is usually either as geodynamic height or as pressure. In oceanology, the most important coordinate is depth, and this, like heights in the atmosphere, is expressed as metric depth from mean sea level, as geodynamic depth, or as pressure. Only for the earth do we find “static” systems in use, ana even here there is real question as to whether the systems are dynamic or static. So it would seem that our answer to the question, of what kind, of coordinate systems are we seeking, must be that we are looking for the same systems as are used in geophysics, and these systems are dynamic in nature already – that is, their definition involvestime.


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