The structural interactions between T cell receptors and MHC-peptide complexes place physical limits on self-nonself discrimination.

Abstract:

:The activation and expansion of T cells in an antimicrobial immune response is based on the ability of T cell receptors (TCR) to discriminate between MHC-bound peptides derived from different microbial agents as well as self-proteins. However, the specificity of T cells is constrained by the limited number of peptide side chains that are available for TCR binding. By considering the structural requirements for peptide binding to MHC molecules and TCR recognition of MHC-peptide complexes, we demonstrated that human T cell clones could recognize a number of peptides from different organisms that were remarkably distinct in their primary sequence. These peptides were particularly diverse at those sequence positions buried in pockets of the MHC binding site, whereas a higher degree of similarity was present at a limited number of peptide residues that created the interface with the TCR. These T cell clones had been isolated from multiple sclerosis patients with human myelin basic protein, demonstrating that activation of such autoreactive T cells by microbial peptides with sufficient structural similarity may contribute to the disease process. Similar findings have now been made for a variety of human and murine T cell clones, indicating that specificity and cross-reactivity are inherent properties of TCR recognition. The observations that particular TCR are highly sensitive to changes at particular peptide positions but insensitive to many other changes in peptide sequence are not contradictory, but rather the result of structural interactions in which a relatively flat TCR surface contacts a limited number of side chains from a peptide that is deeply embedded in the MHC binding site.

authors

Wucherpfennig KW

doi

10.1007/3-540-30791-5_2

subject

Has Abstract

pub_date

2005-01-01 00:00:00

pages

19-37

eissn

0070-217X

issn

2196-9965

journal_volume

296

pub_type

杂志文章,评审
  • Role of Dicer in posttranscriptional RNA silencing.

    abstract::Dicer, an RNase III type endonuclease, is the key enzyme involved in RNA interference (RNAi) and microRNA (miRNA) pathways. It is required for biogenesis of miRNAs and small interfering RNAs (siRNAs), and also plays an important role in an effector step of RNA silencing, the RNA-induced silencing complex (RISC) assemb...

    journal_title:Current topics in microbiology and immunology

    pub_type: 杂志文章,评审

    doi:10.1007/978-3-540-75157-1_4

    authors: Jaskiewicz L,Filipowicz W

    更新日期:2008-01-01 00:00:00

  • Why and How Epstein-Barr Virus Was Discovered 50 Years Ago.

    abstract::An account is given of the experiences and events which led to a search being undertaken for a causative virus in the recently described Burkitt's lymphoma and of the steps which ultimately culminated in the discovery of the new human herpesvirus which came to be known as Epstein-Barr virus (EBV). ...

    journal_title:Current topics in microbiology and immunology

    pub_type: 历史文章,杂志文章,评审

    doi:10.1007/978-3-319-22822-8_1

    authors: Epstein A

    更新日期:2015-01-01 00:00:00

  • Bats, civets and the emergence of SARS.

    abstract::Severe acute respiratory syndrome (SARS) was the first pandemic transmissible disease of previously unknown aetiology in the twenty-first century. Early epidemiologic investigations suggested an animal origin for SARS-CoV. Virological and serological studies indicated that masked palm civets ( Paguma larvata), togethe...

    journal_title:Current topics in microbiology and immunology

    pub_type: 杂志文章,评审

    doi:10.1007/978-3-540-70962-6_13

    authors: Wang LF,Eaton BT

    更新日期:2007-01-01 00:00:00

  • B cell recruitment and selection in mouse GALT germinal centers.

    abstract::In conventionally reared mice germinal centers (GCs) are chronically induced in Peyer's patches (PP), mesenteric lymph node (MLN), and isolated lymphoid follicles (ILF) of gut-associated lymphoid tissues (GALT), as a result of continuous B cell stimulation by commensal bacteria. It is generally thought that BCR-mediat...

    journal_title:Current topics in microbiology and immunology

    pub_type: 杂志文章,评审

    doi:10.1007/3-540-30657-9_7

    authors: Casola S,Rajewsky K

    更新日期:2006-01-01 00:00:00

  • Human Organotypic Models for Anti-infective Research.

    abstract::The use of human organotypic models for biomedical research is experiencing a significant increase due to their biological relevance, the possibility to perform high-throughput analyses, and their cost efficiency. In the field of anti-infective research, comprising the search for novel antipathogenic treatments includ...

    journal_title:Current topics in microbiology and immunology

    pub_type: 杂志文章

    doi:10.1007/82_2018_130

    authors: Hendriks A,Cruz AR,Soldaini E,Manetti AGO,Bagnoli F

    更新日期:2018-09-20 00:00:00

  • Evolution and ecology of influenza A viruses.

    abstract::Wild aquatic bird populations have long been considered the natural reservoir for influenza A viruses with virus transmission from these birds seeding other avian and mammalian hosts. While most evidence still supports this dogma, recent studies in bats have suggested other reservoir species may also exist. Extensive ...

    journal_title:Current topics in microbiology and immunology

    pub_type: 杂志文章,评审

    doi:10.1007/82_2014_396

    authors: Yoon SW,Webby RJ,Webster RG

    更新日期:2014-01-01 00:00:00

  • Antimicrobial peptides versus invasive infections.

    abstract::It has been estimated that there are more microorganisms within and upon the human body than there are human cells. By necessity, every accessible niche must be defended by innate mechanisms to prevent invasive infection, and ideally that precludes the need for robust inflammatory responses. Yet the potential for path...

    journal_title:Current topics in microbiology and immunology

    pub_type: 杂志文章,评审

    doi:10.1007/3-540-29916-5_5

    authors: Yeaman MR,Bayer AS

    更新日期:2006-01-01 00:00:00

  • Genetic dissection of host resistance to Mycobacterium tuberculosis: the sst1 locus and the Ipr1 gene.

    abstract::Genetic variation of the host significantly contributes to dramatic differences in the outcomes of natural infection with virulent Mycobacterium tuberculosis (MTB) in humans, as well as in experimental animal models. Host resistance to tuberculosis is a complex multifactorial genetic trait in which many genetic polymo...

    journal_title:Current topics in microbiology and immunology

    pub_type: 杂志文章,评审

    doi:10.1007/978-3-540-75203-5_6

    authors: Kramnik I

    更新日期:2008-01-01 00:00:00

  • Ecological aspects of hendra virus.

    abstract::Hendra virus, a novel and fatally zoonotic member of the family Paramyxoviridae, was first described in Australia in 1994. Periodic spillover from its natural host (fruit bats) results in catastrophic disease in horses and occasionally the subsequent infection of humans. Prior to 2011, 14 equine incidents involving se...

    journal_title:Current topics in microbiology and immunology

    pub_type: 杂志文章,评审

    doi:10.1007/82_2012_214

    authors: Field H,Crameri G,Kung NY,Wang LF

    更新日期:2012-01-01 00:00:00

  • Immunization strategies against henipaviruses.

    abstract::Hendra virus and Nipah virus are recently discovered and closely related emerging viruses that now comprise the genus henipavirus within the sub-family Paramyxoviridae and are distinguished by their broad species tropism and in addition to bats can infect and cause fatal disease in a wide variety of mammalian hosts in...

    journal_title:Current topics in microbiology and immunology

    pub_type: 杂志文章,评审

    doi:10.1007/82_2012_213

    authors: Broder CC,Geisbert TW,Xu K,Nikolov DB,Wang LF,Middleton D,Pallister J,Bossart KN

    更新日期:2012-01-01 00:00:00

  • Sweet and sour: the role of glycosylation for the anti-inflammatory activity of immunoglobulin G.

    abstract::The importance of immunoglobulin G (IgG) molecules for providing long-term sterile immunity as well as their major contribution to tissue inflammation during autoimmune diseases is generally accepted. In a similar manner, studies over the last years have elucidated many details of the molecular and cellular pathways u...

    journal_title:Current topics in microbiology and immunology

    pub_type: 杂志文章,评审

    doi:10.1007/978-3-319-07911-0_18

    authors: Böhm S,Kao D,Nimmerjahn F

    更新日期:2014-01-01 00:00:00

  • Visualizing intermolecular interactions in T cells.

    abstract::The use of appropriate fluorescent proteins has allowed the use of FRET microscopy for investigation of intermolecular interactions in living cells. This method has the advantage of both being dynamic and of working at the subcellular level, so that the time and place where proteins interact can be visualized. We have...

    journal_title:Current topics in microbiology and immunology

    pub_type: 杂志文章,评审

    doi:10.1007/978-3-540-93864-4_2

    authors: Gascoigne NR,Ampudia J,Clamme JP,Fu G,Lotz C,Mallaun M,Niederberger N,Palmer E,Rybakin V,Yachi PP,Zal T

    更新日期:2009-01-01 00:00:00

  • The APOBEC3 family of retroelement restriction factors.

    abstract::The ability to regulate and even target mutagenesis is an extremely valuable cellular asset. Enzyme-catalyzed DNA cytosine deamination is a molecular strategy employed by vertebrates to promote antibody diversity and defend against foreign nucleic acids. Ten years ago, a family of cellular enzymes was first described ...

    journal_title:Current topics in microbiology and immunology

    pub_type: 杂志文章,评审

    doi:10.1007/978-3-642-37765-5_1

    authors: Refsland EW,Harris RS

    更新日期:2013-01-01 00:00:00

  • The neurodevelopmental implications of PI3K signaling.

    abstract::Our understanding of the mechanisms involved in the formation of the complex arrangement of neurons and their interconnections within the brain has made significant progress in recent years. Current research has uncovered a network of intracellular signaling events that provide precise coordination of a diverse array ...

    journal_title:Current topics in microbiology and immunology

    pub_type: 杂志文章,评审

    doi:10.1007/82_2010_82

    authors: Waite K,Eickholt BJ

    更新日期:2010-01-01 00:00:00

  • Swine atrophic rhinitis caused by pasteurella multocida toxin and bordetella dermonecrotic toxin.

    abstract::Atrophic rhinitis is a widespread and economically important swine disease caused by Pasteurella multocida and Bordetella bronchiseptica. The disease is characterized by atrophy of the nasal turbinate bones, which results in a shortened and deformed snout in severe cases. P. multocida toxin and B. bronchiseptica dermo...

    journal_title:Current topics in microbiology and immunology

    pub_type: 杂志文章,评审

    doi:10.1007/82_2012_206

    authors: Horiguchi Y

    更新日期:2012-01-01 00:00:00

  • Cholera outbreaks in South-East Asia.

    abstract::This chapter highlights the cholera situation in South Asia and the Bay of Bengal region, the original 'homeland' of cholera. A detailed discussion of cholera outbreaks in individual countries in South-East Asia follows. The countries of the World Health Organization (WHO) SEARO (South-East Asia Region) region are dis...

    journal_title:Current topics in microbiology and immunology

    pub_type: 杂志文章,评审

    doi:10.1007/82_2014_362

    authors: Bharati K,Bhattacharya SK

    更新日期:2014-01-01 00:00:00

  • Assembly and Function of the Precursor B-Cell Receptor.

    abstract::During early stages of development, precursor B lymphocytes express a characteristic type of antigen receptor known as the pre-B-cell receptor (pre-BCR). This receptor differs from conventional BCRs in that it possesses a germ line-encoded surrogate light chain (SLC), which is associated with the signal transduction m...

    journal_title:Current topics in microbiology and immunology

    pub_type: 杂志文章,评审

    doi:10.1007/82_2015_475

    authors: Übelhart R,Werner M,Jumaa H

    更新日期:2016-01-01 00:00:00

  • Regulation of splicing by protein phosphorylation.

    abstract::Most eukaryotic messenger RNAs are transcribed as precursors that necessitate specific and exact processing of intron boundaries. Furthermore, the choice of these boundaries appears to be fluid and adaptive to the rate of transcription and the developmental and physiological state of the cell. A central regulator of s...

    journal_title:Current topics in microbiology and immunology

    pub_type: 杂志文章,评审

    doi:10.1007/978-3-540-76776-3_7

    authors: Fluhr R

    更新日期:2008-01-01 00:00:00

  • Physiological functions of autophagy.

    abstract::The field of autophagy research has advanced rapidly in recent years, with important discoveries made in relation to both molecular mechanisms and physiological functions. Initially, autophagy was thought to be primarily a response to starvation. Although this might be true in lower eukaryotes, this catabolic process ...

    journal_title:Current topics in microbiology and immunology

    pub_type: 杂志文章,评审

    doi:10.1007/978-3-642-00302-8_3

    authors: Mizushima N

    更新日期:2009-01-01 00:00:00

  • DNA methylation profiles of female steroid hormone-driven human malignancies.

    abstract::Tumor DNA contains valuable clues about the origin and pathogenesis of human cancers. Alterations in DNA methylation can lead to silencing of genes associated with distinct tumorigenic pathways. These pathway-specific DNA methylation changes help define tumor-specific DNA methylation profiles that can be used to furth...

    journal_title:Current topics in microbiology and immunology

    pub_type: 杂志文章,评审

    doi:10.1007/3-540-31181-5_8

    authors: Campan M,Weisenberger DJ,Laird PW

    更新日期:2006-01-01 00:00:00

  • EBNA1.

    abstract::Epstein-Barr nuclear antigen 1 (EBNA1) plays multiple important roles in EBV latent infection and has also been shown to impact EBV lytic infection. EBNA1 is required for the stable persistence of the EBV genomes in latent infection and activates the expression of other EBV latency genes through interactions with spec...

    journal_title:Current topics in microbiology and immunology

    pub_type: 杂志文章,评审

    doi:10.1007/978-3-319-22834-1_1

    authors: Frappier L

    更新日期:2015-01-01 00:00:00

  • Chloroplast-derived vaccine antigens and biopharmaceuticals: expression, folding, assembly and functionality.

    abstract::Chloroplast genetic engineering offers several advantages, including high levels of transgene expression, transgene containment via maternal inheritance, and multi-gene expression in a single transformation event. Oral delivery is facilitated by hyperexpression of vaccine antigens against cholera, tetanus, anthrax, pl...

    journal_title:Current topics in microbiology and immunology

    pub_type: 杂志文章,评审

    doi:10.1007/978-3-540-70868-1_3

    authors: Chebolu S,Daniell H

    更新日期:2009-01-01 00:00:00

  • Remyelination-promoting human IgMs: developing a therapeutic reagent for demyelinating disease.

    abstract::Promoting remyelination following injury to the central nervous system (CNS) promises to be an effective neuroprotective strategy to limit the loss of surviving axons and prevent disability. Studies confirm that multiple sclerosis (MS) and spinal cord injury lesions contain myelinating cells and their progenitors. Rec...

    journal_title:Current topics in microbiology and immunology

    pub_type: 杂志文章,评审

    doi:10.1007/978-3-540-73677-6_9

    authors: Warrington AE,Rodriguez M

    更新日期:2008-01-01 00:00:00

  • The CD4/CD8 lineages: central decisions and peripheral modifications for T lymphocytes.

    abstract::CD4(+) helper and CD8(+) cytotoxic T cells, two major subsets of αβTCR expressing lymphocytes, are differentiated from common precursor CD4(+)CD8(+) double-positive (DP) thymocytes. Bifurcation of the CD4(+)/CD8(+) lineages in the thymus is a multilayered process and is thought to culminate in a loss of developmental ...

    journal_title:Current topics in microbiology and immunology

    pub_type: 杂志文章,评审

    doi:10.1007/82_2013_323

    authors: Tanaka H,Taniuchi I

    更新日期:2014-01-01 00:00:00

  • Human airway epithelial cell cultures for modeling respiratory syncytial virus infection.

    abstract::Respiratory syncytial virus (RSV) is an important human respiratory pathogen with narrow species tropism. Limited availability of human pathologic specimens during early RSV-induced lung disease and ethical restrictions for RSV challenge studies in the lower airways of human volunteers has slowed our understanding of ...

    journal_title:Current topics in microbiology and immunology

    pub_type: 杂志文章

    doi:10.1007/978-3-642-38919-1_19

    authors: Pickles RJ

    更新日期:2013-01-01 00:00:00

  • Subversion of cell cycle regulatory pathways.

    abstract::Human cytomegalovirus (HCMV) has evolved numerous strategies to commandeer the host cell for producing viral progeny. The virus manipulates host cell cycle pathways from the early stages of infection to stimulate viral DNA replication at the expense of cellular DNA synthesis. At the same time, cell cycle checkpoints a...

    journal_title:Current topics in microbiology and immunology

    pub_type: 杂志文章,评审

    doi:10.1007/978-3-540-77349-8_14

    authors: Sanchez V,Spector DH

    更新日期:2008-01-01 00:00:00

  • VZV T cell-mediated immunity.

    abstract::Primary varicella-zoster virus (VZV) infection (varicella) induces VZV-specific antibody and VZV-specific T cell-mediated immunity. T cell-mediated immunity, which is detected within 1-2 weeks after appearance of rash, and consists of both CD4 and CD8 effector and memory T cells, is essential for recovery from varicel...

    journal_title:Current topics in microbiology and immunology

    pub_type: 杂志文章,评审

    doi:10.1007/82_2010_31

    authors: Weinberg A,Levin MJ

    更新日期:2010-01-01 00:00:00

  • Introduction to the E2F family: protein structure and gene regulation.

    abstract::E2F is a heterodimer composed of two partners, such as E2F1 and DP1. Although E2F1 can bind DNA as a homodimer and increase promoter activity, optimal DNA-binding and transcriptional activity occurs in the heterodimeric form. A model (Fig. 3) for the involvement of E2F activity in cell growth control that incorporates...

    journal_title:Current topics in microbiology and immunology

    pub_type: 杂志文章,评审

    doi:10.1007/978-3-642-79910-5_1

    authors: Slansky JE,Farnham PJ

    更新日期:1996-01-01 00:00:00

  • The foamy virus envelope glycoproteins.

    abstract::The main functions of retroviral glycoproteins are recognition and binding to the cellular virus receptor as well as fusion of viral and cellular lipid membranes to release the viral particle into the cytoplasm of the host cell. Foamy viruses (FVs) are a special group of retroviruses with a very broad host range that ...

    journal_title:Current topics in microbiology and immunology

    pub_type: 杂志文章,评审

    doi:10.1007/978-3-642-55701-9_5

    authors: Lindemann D,Goepfert PA

    更新日期:2003-01-01 00:00:00

  • Risk and Response to Biological Catastrophe in Lower Income Countries.

    abstract::Natural and intentional biological risks threaten human civilization, both through direct human fatality as well as follow-on effects from a collapse of the just-in-time delivery system that provides food, energy and critical supplies to communities globally. Human beings have multiple innate cognitive biases that sys...

    journal_title:Current topics in microbiology and immunology

    pub_type: 杂志文章,评审

    doi:10.1007/82_2019_162

    authors: Luby S,Arthur R

    更新日期:2019-01-01 00:00:00