Abstract:
:Dynamics plays an important but underappreciated role in the interaction between the T cell receptor (TCR) and peptide-bound major histocompatibility complex (pMHC). Crystallographic studies have provided key molecular insights into this interaction; however, due to inherent features of the structural approach, the image of TCR-pMHC interactions that has emerged is a static one. In this review, we discuss how molecular dynamics (MD) simulations can complement and extend current experimental methods aimed at examining TCR-pMHC dynamics. We review the insights obtained from studies that leverage MD approaches, and propose that an integrative strategy that harnesses both MD simulations and structural and biophysical methods will provide new inroads into understanding the transitory and dynamic molecular events that dictate TCR signaling and T cell activation.
journal_name
Trends Immunoljournal_title
Trends in immunologyauthors
Kass I,Buckle AM,Borg NAdoi
10.1016/j.it.2014.10.005subject
Has Abstractpub_date
2014-12-01 00:00:00pages
604-612issue
12eissn
1471-4906issn
1471-4981pii
S1471-4906(14)00190-2journal_volume
35pub_type
评审abstract::Recent advances in the understanding of medullary thymic epithelial cell biology, and especially of their promiscuous gene expression, have highlighted the indispensable role of thymic medulla in shaping a self-tolerant T-cell repertoire. Additionally, our recent results have shown that cortical thymic epithelial cell...
journal_title:Trends in immunology
pub_type: 杂志文章,评审
doi:10.1016/j.it.2008.03.003
更新日期:2008-06-01 00:00:00
abstract::The mechanisms underlying the failure to control the growth and systemic spread of Leishmania parasites in human visceral leishmaniasis (VL) are not well understood. Although the absence of antigen-specific Th1 responses in the peripheral blood mononuclear cells from VL patients is thought to be causally related to di...
journal_title:Trends in immunology
pub_type: 杂志文章,评审
doi:10.1016/j.it.2007.07.004
更新日期:2007-09-01 00:00:00
abstract::Recent studies have uncovered sterile alpha motif and HD domain 1 (SAMHD1) as the restriction factor that blocks HIV-1 replication in myeloid cells. In contrast to previously identified HIV-1 restriction factors, SAMHD1 does not meet a countermeasure developed by HIV-1. However, HIV-2 and certain simian immunodeficien...
journal_title:Trends in immunology
pub_type: 杂志文章,评审
doi:10.1016/j.it.2011.11.002
更新日期:2012-01-01 00:00:00
abstract::Inducing sustained, robust CD8(+) T cell responses is necessary for therapeutic intervention in chronic infectious diseases and cancer. Unfortunately, most adjuvant formulations fail to induce substantial cellular immunity in humans. Attenuated acute infectious agents induce strong CD8(+) T cell immunity, and are thou...
journal_title:Trends in immunology
pub_type: 杂志文章,评审
doi:10.1016/j.it.2016.01.001
更新日期:2016-03-01 00:00:00
abstract::T cells, as orchestrators of the adaptive immune response, serve important physiological and potentially therapeutic roles, for example in cancer immunotherapy. T cells are readily isolated from patients; however, the yield of antigen-specific T cells is limited, thus making their clinical use challenging. Therefore, ...
journal_title:Trends in immunology
pub_type: 杂志文章,评审
doi:10.1016/j.it.2016.09.008
更新日期:2016-12-01 00:00:00
abstract::During an immune response, peripheral T-cell populations expand and then contract as the response subsides, thus maintaining a fairly constant number of CD4 and CD8 T cells throughout the life of the individual. The important factors that control this homeostasis are now beginning to be understood. Interleukin-7 (IL-7...
journal_title:Trends in immunology
pub_type: 杂志文章,评审
doi:10.1016/j.it.2005.01.004
更新日期:2005-03-01 00:00:00
abstract::CD8+ T cell immunological memory of past antigen exposure can confer long-lived protection against infections or tumors. The fact that CD8+ memory T cells can have features of both naïve and effector cells has forced the field to struggle with several conceptual questions about the developmental origin of the cell and...
journal_title:Trends in immunology
pub_type: 杂志文章,评审
doi:10.1016/j.it.2019.11.004
更新日期:2020-01-01 00:00:00
abstract::Recent advances allow aging-associated changes in B-cell function to be approached at a mechanistic level. Reduced expression of genes crucial to lineage commitment and differentiation yield diminished B-cell production. Moreover, intrinsic differences in the repertoire generated by B-cell precursors in aged individua...
journal_title:Trends in immunology
pub_type: 杂志文章,评审
doi:10.1016/j.it.2009.04.005
更新日期:2009-07-01 00:00:00
abstract::Recent studies have indicated that complement proteins might exert novel functions that are distinct from their well-established inflammatory role, by modulating cellular responses and cell-cell interactions that are crucial to early development and cell differentiation. Accumulating evidence suggests that complement ...
journal_title:Trends in immunology
pub_type: 杂志文章,评审
doi:10.1016/s1471-4906(02)02287-1
更新日期:2002-10-01 00:00:00
abstract::NLRP6, a member of the nucleotide-binding domain, leucine-rich repeat-containing (NLR) innate immune receptor family, regulates inflammation and host defense against microorganisms. Similar to other NLRs, NLRP6 not only participates in inflammasome formation, but is also involved in nuclear factor-κB (NF-κB) and mitog...
journal_title:Trends in immunology
pub_type: 杂志文章,评审
doi:10.1016/j.it.2017.01.001
更新日期:2017-04-01 00:00:00
abstract::Three studies published in Cell Reports (Hinks et al., Lamichhane et al., and Leng et al.) describe the transcriptome of human and mouse mucosal-associated invariant T (MAIT) cells after cognate and noncognate stimulation. The results confirm the variability of MAIT cell effector functions and provide evidence of a ne...
journal_title:Trends in immunology
pub_type: 评论,杂志文章
doi:10.1016/j.it.2019.09.001
更新日期:2019-11-01 00:00:00
abstract::Antigen cross-presentation describes the process through which dendritic cells (DCs) acquire exogenous antigens for presentation on MHC class I molecules. The ability to cross-present has been thought of as a feature of specialized DC subsets. Emerging data, however, suggest that the cross-presenting ability of each D...
journal_title:Trends in immunology
pub_type: 杂志文章
doi:10.1016/j.it.2013.02.007
更新日期:2013-08-01 00:00:00
abstract::Increasing age is associated with a decreasing ability to mediate effective immune responses to newly encountered antigens. It is generally believed that this reflects the age-associated decline in the number, repertoire and function of available naive T cells. Here, we propose that naive T cells become increasingly i...
journal_title:Trends in immunology
pub_type: 杂志文章
doi:10.1016/j.it.2006.05.002
更新日期:2006-07-01 00:00:00
abstract::Recent advances in genome analysis have provided important insights into the genetic architecture of infectious and inflammatory diseases. The combined analysis of loci detected by genome-wide association studies (GWAS) in 22 inflammatory diseases has revealed a shared genetic core and associated biochemical pathways ...
journal_title:Trends in immunology
pub_type: 杂志文章,评审
doi:10.1016/j.it.2015.12.006
更新日期:2016-02-01 00:00:00
abstract::House dust mites (HDM; Dermatophagoides sp.) are one of the commonest aeroallergens worldwide and up to 85% of asthmatics are typically HDM allergic. Allergenicity is associated both with the mites themselves and with ligands derived from mite-associated bacterial and fungal products. Murine models of allergic airways...
journal_title:Trends in immunology
pub_type: 杂志文章,评审
doi:10.1016/j.it.2011.06.006
更新日期:2011-09-01 00:00:00
abstract::Within the 'success story' of vertebrate evolution, the acquisition and refinement of the adaptive immune system is far from the least impressive example of co-evolution. Members of the tumour necrosis factor superfamily (TNFSF) and TNF receptor superfamily (TNFRSF) have crucial roles in both innate and adaptive immun...
journal_title:Trends in immunology
pub_type: 杂志文章,评审
doi:10.1016/s1471-4906(03)00166-2
更新日期:2003-07-01 00:00:00
abstract::A prominent population of innate CD8+ T cells develops in the thymus of several gene-deficient mouse strains, including Itk, KLF2, CBP and Id3. These cells have the phenotype and function of memory CD8+ T cells, without previous exposure to antigen. Surprisingly, the cytokine IL-4 plays a key role in their development...
journal_title:Trends in immunology
pub_type: 杂志文章,评审
doi:10.1016/j.it.2010.12.004
更新日期:2011-02-01 00:00:00
abstract::The human immune system comprises cellular and molecular components designed to coordinately prevent infection while avoiding potentially harmful inflammation and autoimmunity. Immunity varies with age, reflecting unique age-dependent challenges including fetal gestation, the neonatal phase, and infancy. Here, we revi...
journal_title:Trends in immunology
pub_type: 杂志文章,评审
doi:10.1016/j.it.2014.04.007
更新日期:2014-07-01 00:00:00
abstract::Natural killer (NK)-cell receptors (NKRs) on CD8+ T cells can modulate antigen-specific T-cell activity but their function and rules that govern their expression remain unclear. Recent work has provided new insight into CD94-NKG2A expression on T cells. Whereas upregulation on the cell surface is induced following T-c...
journal_title:Trends in immunology
pub_type: 杂志文章
doi:10.1016/s1471-4906(03)00064-4
更新日期:2003-04-01 00:00:00
abstract::Basic immunological research has greatly expanded our understanding of the suspected immunopathology of multiple sclerosis (MS) and, more importantly, spawned a new generation of clinical trials evaluating dozens of immune-based therapies. Adhesion molecules are the furthest into development, although patient acceptan...
journal_title:Trends in immunology
pub_type: 杂志文章,评审
doi:10.1016/j.it.2004.09.012
更新日期:2004-12-01 00:00:00
abstract::The mechanisms accounting for the protective role of endogenous interferon gamma (IFN-gamma) in certain murine autoimmune disease models, versus a disease-promoting role in others, have remained elusive. The protective effect of IFN-gamma might be unique to models that rely on the use of complete Freund's adjuvant (CF...
journal_title:Trends in immunology
pub_type: 杂志文章,评审
doi:10.1016/s1471-4906(01)01937-8
更新日期:2001-07-01 00:00:00
abstract::Three recent studies provide new insight into the mechanisms that promote the differentiation of antigen-primed T cells into the follicular helper T (Tfh) lineage, revealing a key role for the transcription factor TCF-1 in the regulation of the Bcl6-Blimp-1 axis that mediates the divergence between the Tfh and the Th1...
journal_title:Trends in immunology
pub_type: 杂志文章
doi:10.1016/j.it.2015.11.001
更新日期:2015-12-01 00:00:00
abstract::Lymphocyte development has long served as an experimental paradigm, revealing fundamental mechanisms of gene regulation and cellular differentiation in mammals. The study of E-protein-mediated transcriptional regulation in lymphocyte development provides a means to address these mechanistic issues. Both genetic and bi...
journal_title:Trends in immunology
pub_type: 杂志文章,评审
doi:10.1016/j.it.2005.03.011
更新日期:2005-06-01 00:00:00
abstract::Whether MHC restriction by the T cell receptor (TCR) is a product of evolutionary pressures leading to germline-encoded 'rules of engagement' remains avidly debated. Structural results derived from analysis of TCR-peptide-MHC complexes appear to support a model of physical specificity between TCR germline V regions an...
journal_title:Trends in immunology
pub_type: 杂志文章
doi:10.1016/j.it.2012.05.005
更新日期:2012-09-01 00:00:00
abstract::Epigenetic marks, such as DNA methylation, histone post-translational modifications and miRNAs, are induced in B cells by the same stimuli that drive the antibody response. They play major roles in regulating somatic hypermutation (SHM), class switch DNA recombination (CSR), and differentiation to plasma cells or long...
journal_title:Trends in immunology
pub_type: 杂志文章,评审
doi:10.1016/j.it.2013.03.006
更新日期:2013-09-01 00:00:00
abstract::CD45, the leucocyte common antigen, is a haemopoietic cell-specific tyrosine phosphatase. Many isoforms are generated by alternative splicing, but their function remains obscure. The extracellular domain of CD45 is highly polymorphic in all vertebrates. Importantly, human polymorphic variants that alter CD45 isoform e...
journal_title:Trends in immunology
pub_type: 杂志文章,评审
doi:10.1016/j.it.2006.01.001
更新日期:2006-03-01 00:00:00
abstract::The ocular surface is a unique mucosal immune compartment in which anatomical, physiological, and immunological features act in concert to foster a particularly tolerant microenvironment. These mechanisms are vital to the functional competence of the eye, a fact underscored by the devastating toll of excessive inflamm...
journal_title:Trends in immunology
pub_type: 杂志文章,评审
doi:10.1016/j.it.2017.11.007
更新日期:2018-04-01 00:00:00
abstract::In lymphatic tissue, professional antigen-presenting cells (APCs) such as dendritic cells (DCs), mature after sensing microbe-associated molecular patterns (MAMPs) by pattern recognition receptors (PRRs), and subsequently activate T cell immunity. Non-pathogenic MAMPs, derived for example from commensal bacteria, are ...
journal_title:Trends in immunology
pub_type: 杂志文章,评审
doi:10.1016/j.it.2010.06.001
更新日期:2010-08-01 00:00:00
abstract::Microglia are brain macrophages that emerge from early erythro-myeloid precursors in the embryonic yolk sac and migrate to the brain mesenchyme before the blood brain barrier is formed. They seed the brain, and proliferate until they have formed a grid-like distribution in the central nervous system that is maintained...
journal_title:Trends in immunology
pub_type: 杂志文章,评审
doi:10.1016/j.it.2015.08.005
更新日期:2015-10-01 00:00:00
abstract::The workshop on Multiple Sclerosis and Chemokines: Prospects for Therapeutic and Prophylactic Intervention was held in Chevy Chase, MD, USA, from 9-10 July 2001. ...
journal_title:Trends in immunology
pub_type:
doi:10.1016/s1471-4906(01)02056-7
更新日期:2001-11-01 00:00:00