Polyspecificity of T cell and B cell receptor recognition

Wucherpfennig, Kai W.; Allen, Paul M.; Celada, Franco; Cohen, Irun R.; Boer, Rob de; García, K. Christopher; Goldstein, Byron; Greenspan, Ralph J.; Hafler, David A.; Hodgkin, Philip D.; Huseby, Erik S.; Krakauer, David C.; Nemazee, David; Perelson, Alan S.; Pinilla, Clemencia; Strong, Roland K.; Sercarz, Eli E.

doi:10.1016/j.smim.2007.02.012

Cited by 194 publications

(180 citation statements)

References 46 publications

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“…EcIF1 was coated at 0.5 g/well to microtiter plates, plates were washed, and then EcIF1 (33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46) was added at concentrations between 6.6 ϫ 10 2 and 3.3 ϫ 10 Ϫ4 g/ml together with M88-transfected hybridoma cells. Recognition of EcIF1 was not influenced by the synthetic peptide EcIF1 (33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46). C, wild-type EcIF1 was denatured by exposure to 6 M guanidinium thiocyante (Gua ϩ SCN Ϫ ), 2 M HCl, 5 M NaOH.…”

Section: Discussionmentioning

confidence: 99%

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Target Specificity of an Autoreactive Pathogenic Human γδ-T Cell Receptor in Myositis

Bruder

Siewert

Obermeier

et al. 2012

Journal of Biological Chemistry

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Background:In a rare case of human autoimmune myositis, muscle fibers are attacked by ␥␦-T cells. Results: We identified several antigens recognized by the ␥␦-T cell receptor. Conclusion:The ␥␦-T cell receptor recognized human tRNA synthetases known as antigens of autoantibodies in myositis. Significance: This is the first report of an antigen recognized by human ␥␦-T cells in an autoimmune disease.

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Section: Discussionmentioning

confidence: 99%

“…Peptides, Proteins, and Antibodies-The synthetic peptide EcIF1 (33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46), which represents amino acids 33-46 of EcIF1, was synthesized by solid phase peptide synthesis and purified by reversed phase HPLC. Its correct sequence was verified by mass spectrometry.…”

Section: Methodsmentioning

confidence: 99%

Target Specificity of an Autoreactive Pathogenic Human γδ-T Cell Receptor in Myositis

Bruder

Siewert

Obermeier

et al. 2012

Journal of Biological Chemistry

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“…In spite of this fact, the two peptides may share common binding motifs, dictated by structural requirements of the HLA pockets accommodating the peptides. Due to the degenerate nature of the HLA binding and TCR recognition, an observation which has been widely accepted for the past decade, 94 common binding motifs would be sufficient to allow peptide binding to different HLA molecules. However, in this case, it is possible that the recognition of the HLA/peptide complex by T cells will differ depending on the orientation of the TCR interacting with the amino acids facing away from the binding groove, and thus will result in differential activation by T cells.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics-Based Predictions of Peptide Binding to Disease-Associated HLA Proteins Suggest Explanation for Shared Autoimmunity

Glutting

Reche

Fridkis-Hareli³

2011

Immunol Immunogenet Insights

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Abstract:Aim: This study was designed to examine the immunogenetic basis for shared autoimmunity, resulting in autoantigen presentation that leads to the production of two or more disease-specific autoantibodies. Methods: A bioinformatics approach based on peptide binding predictions to disease-associated HLA determinants has been developed and tested here using 11 disease associations between autoimmune systemic and mucocutaneous blistering disorders. Various HLAs associated with antigens within a given "disease model" (set of HLA class II and protein sequences known to be associated with a specific autoimmune disease) were tested and ranked against the antigenic proteins, first with proteins they are known to associate with and then with proteins known to be implicated in a second disease model. In every case binding predictions were compared for different proteins binding to the same HLA. Subsequently, disease-related autoantigens have been tested for their binding affinity against each disease-specific HLA class II protein.Results: For a single HLA haplotype, several binders have been generated from a related autoantigen with the variable binding score. In most cases, the binding score corresponding to the interactions between the autoantigen-derived epitope and the HLA associated with one disease was similar or lower than the interactions between the epitope from proteins associated with the second disease and the same HLA. Notably, there was no compelling promiscuity in peptide binding to each of the HLA molecules, in spite of the promiscuous nature of HLA class II binding. Conclusions:The data suggest that, in susceptible individuals, shared autoimmunity might be initiated by two types of HLA/peptide interaction; first between an autoantigen-derived epitope and its disease-associated HLA molecules, and second, between a different peptide of the same autoantigen and HLA proteins specific for the second disease.

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“…A ''codon hypothesis'' which suggests that each TCR variable-region gene product engages each type of MHC through a ''menu'' of structurally coded recognition motifs that have arisen through coevolution has been proposed to clarify the existence of ''TCR-MHC bias'' or ''germlineencoded recognition'' of MHC. Here, ''bias'' is simply a euphemism for specificity, and cases of true cross-reactivity are more correctly called ''polyspecificity'' (14). ''Induce-fit'' interaction mode facilitates polyspecificity to occur which is usually seen in the immune system of specific recognition by one protein of a spectrum of diverse ligands.…”

Section: Specificity Determined By Interaction Of Ab T Cell Receptorsmentioning

confidence: 99%

Structural immunology and crystallography help immunologists see the immune system in action: How T and NK cells touch their ligands

et al. 2009

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SummaryHost immune system is an important and sophisticated system, maintaining the balance of host response to ''foreign'' antigens and ignorance to the normal-self. To fulfill this achievement the system manipulates a cell-cell interaction through appropriate interactions between cell-surface receptors and cellsurface ligands, or cell-secreted soluble effector molecules to their ligands/receptors/counter-receptors on the cell surface, triggering further downstream signaling for response effects. T cells and NK cells are important components of the immune system for defending the infections and malignancies and maintaining the proper response against over-reaction to the host. Receptors on the surface of T cells and NK cells include a number of important protein molecules, for example, T cell receptor (TCR), co-receptor CD8 or CD4, co-stimulator CD28, CTLA4, KIR, CD94/NKG2, LILR (ILT/LIR/CD85), Ly49, and so forth. These receptor molecules interact with their ligands on the target cells, including major histocompatibility complex (MHC) (or human leukocyte antigen, HLA), CD80, CD86, and so forth. Detailed understanding of these receptor-ligand pair interactions is crucial for our full knowledge of the immune system, ultimately for us to manipulate the T cell and NK cell functions. Accumulations of the receptor-ligand complex crystal structures in the recent years have provided us a unique angel to see how the immune cells interacting with their partner cells. In this review, we discussed binding specificity, plasticity, and flexibility of the T cell and NK cell receptor/ligand interaction, fitting the structural data with their functions. Structural immunology indeed helps us see how T and NK cells ''touch'' their target cells in our immune system.

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Polyspecificity of T cell and B cell receptor recognition

Cited by 194 publications

References 46 publications

Target Specificity of an Autoreactive Pathogenic Human γδ-T Cell Receptor in Myositis

Target Specificity of an Autoreactive Pathogenic Human γδ-T Cell Receptor in Myositis

Bioinformatics-Based Predictions of Peptide Binding to Disease-Associated HLA Proteins Suggest Explanation for Shared Autoimmunity

Structural immunology and crystallography help immunologists see the immune system in action: How T and NK cells touch their ligands

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