The Influence of T Cell Development on Pathogen Specificity and Autoreactivity

  title={The Influence of T Cell Development on Pathogen Specificity and Autoreactivity},
  author={Andrej Ko{\vs}mrlj and Mehran Kardar and Arup K. Chakraborty},
  journal={Journal of Statistical Physics},
T cells orchestrate adaptive immune responses upon activation. T cell activation requires sufficiently strong binding of T cell receptors on their surface to short peptides derived from foreign proteins bound to protein products of the major histocompatibility (MHC) gene products, which are displayed on the surface of antigen presenting cells. T cells can also interact with peptide-MHC complexes, where the peptide is derived from host (self) proteins. A diverse repertoire of relatively self… 
6 Citations
Influence of correlated antigen presentation on T-cell negative selection in the thymus
The results suggest that heterogeneity of gene co-expression in mTECs has an effect on the probability of escape of autoreactive thymocytes, and correlated patterns of peptide presentation may be advantageous in negatively selecting low-degeneracyThymocytes.
Statistical Physics of T-Cell Development and Pathogen Specificity
In addition to an innate immune system that battles pathogens in a nonspecific fashion, higher organisms, such as humans, possess an adaptive immune system to combat diverse (and evolving) microbial
Immunological Recognition by Artificial Neural Networks
This work confirmed that ANNs could learn the immunological recognition of TCRs and peptide sequences and found that a homogenized encoding of amino acid sequence was more effective for the supervised learning task.
Artificial neural networks for immunological recognition
This work examined whether the affinity-based discrimination of peptide sequences is learnable and generalizable by artificial neural networks that process the digital information of receptors and peptides and successfully captured the relevant information of molecular interactions and discriminated between strong and weak affinity pairs.
A Complete Bibliography of the Journal of Statistical Physics: 2000{2009
(2 + 1) [XTpXpH12, CTH11]. + [Zuc11b]. 0 [Fed17]. 1 [BELP15, CAS11, Cor16, Fed17, GDL10, GBL16, Hau16, JV19, KT12, KM19c, Li19, MN14b, Nak17, Pal11, Pan14, RT14, RBS16b, RY12, SS18c, Sug10, dOP18]. 1


How the thymus designs antigen-specific and self-tolerant T cell receptor sequences
A dominant role for negative selection in mediating antigen specificity of mature T cells and a molecular mechanism for TCR recognition of antigen are described.
How the T Cell Repertoire Becomes Peptide and MHC Specific
Thymic selection of T-cell receptors as an extreme value problem.
Thymic selection processes are mapped to an extreme value problem and an analytic expression for the amino acid compositions of selected T-cell receptors (which enable its recognition functions) are provided.
A quantitative theory of affinity-driven T cell repertoire selection.
The role of the MHC and peptide contribution to TCR binding is analysed, and it is found that their relative, rather than absolute value, is important in shaping the mature repertoire.
The why and how of thymocyte negative selection.
Explaining high alloreactivity as a quantitative consequence of affinity-driven thymocyte selection.
  • V. Detours, A. Perelson
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1999
The results show that the affinity model of T cell selection can quantitatively explain both self MHC restriction and high alloreactivity.
The effects of thymic selection on the range of T cell cross‐reactivity
Based on the results of a computational model of thymic selection, a mechanism that produces the observed wide range of T cell cross‐reactivity is proposed that is correlated with its affinity for self peptides.
A constant affinity threshold for T cell tolerance
Using three transgenic mouse strains expressing distinct class I MHC–restricted T cell receptors, the affinity that defines the threshold for negative selection appears to be a constant for cytotoxic T lymphocytes.
Antigen-presenting function of the macrophage.
  • E. Unanue
  • Biology
    Annual review of immunology
  • 1984
The available information leads one to conclude that APC deficient in their capacity to internalize and process proteins will not be able to present them, and the macrophage is the candidate as the major APC involved in the recruitment and enlargement of clones T cells.
Thymic selection threshold defined by compartmentalization of Ras/MAPK signalling
It is shown that, at the selection threshold, a small increase in ligand affinity for the T-cell antigen receptor leads to a marked change in the activation and subcellular localization of Ras and mitogen-activated protein kinase (MAPK) signalling intermediates and the induction of negative selection.