Antigenic peptide binding by class I and class II histocompatibility proteins

Stern, Lawrence J.; Wiley, Don C.

doi:10.1016/s0969-2126(00)00026-5

Cited by 291 publications

(185 citation statements)

References 31 publications

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“…Given this, a wide range of different peptides may be expected to bind with class II molecules, and the unfavorable interactions between amino acid side chains and MHC can be countered and stabilized by the wide network of backbone hydrogen bonding with MHC class II molecules (reviewed in Ref. 39). It is still not clear how a given promiscuous peptide binds to different class II MHC molecules.…”

Section: Discussionmentioning

confidence: 99%

Flexibility in MHC and TCR Recognition: Degenerate Specificity at the T Cell Level in the Recognition of Promiscuous Th Epitopes Exhibiting No Primary Sequence Homology

Joshi

Suresh

Chauhan

2001

The Journal of Immunology

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Recognition of peptide Ags by T cells through the TCR can be highly specific. In this report we show the degeneracy of Ag recognition at both MHC and TCR levels. We present evidence that unrelated promiscuous Th cell epitopes from various protein sources exhibit sufficient structural homology, despite minimal structural identity, to elicit cross-reactive proliferative responses at the bulk T cell level. This epitopic mimicry was also observed when peptide (CS.T3378–395 and TT830–844)-specific CD4+ T cell lines and T cell hybridoma clones were used in proliferation and Ag presentation assays. A scrambled CS.T3378–395 peptide did not show any proliferation, indicating that the specificity of the cross-reactive responses may be linked with the primary structure of the peptides. Blocking of CS.T3378–395-specific CD4+ T cell proliferation by anti-MHC class II mAb showed that recognition of promiscuous T cell epitopes is largely in association with MHC class II molecules. These findings suggest that promiscuous Th epitopes may be useful in designing peptide-based vaccine constructs. At the same time these results show that at the T cell level there may be a great deal of immunological cross-reactivity between heterologous pathogens, and because of this the host’s response to a pathogen may be modified by its previous experience with other unrelated pathogens.

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Section: Discussionmentioning

confidence: 99%

Flexibility in MHC and TCR Recognition: Degenerate Specificity at the T Cell Level in the Recognition of Promiscuous Th Epitopes Exhibiting No Primary Sequence Homology

Joshi

Suresh

Chauhan

2001

The Journal of Immunology

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“…If TCRs are prebiased to interact with MHC proteins, essential genetic elements have to be shared between all MHC proteins. It has been appreciated for some time that the overall structure of MHC proteins and their bound peptide is quite similar (Stern and Wiley 1994). Likely because of selective pressure by pathogens, the vast majority of allelic variation between MHC proteins is located within the peptide binding groove (Bjorkman et al 1987).…”

Section: Structural Insights Into the Mechanism Of Mhc Restrictionmentioning

confidence: 99%

Structural Biology of the T-cell Receptor: Insights into Receptor Assembly, Ligand Recognition, and Initiation of Signaling

Wucherpfennig¹,

Gagnon²,

Call³

et al. 2010

Cold Spring Harbor Perspectives in Biology

154

108

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The T-cell receptor (TCR)-CD3 complex serves as a central paradigm for general principles of receptor assembly, ligand recognition, and signaling in the immune system. There is no other receptor system that matches the diversity of both receptor and ligand components. The recent expansion of the immunological structural database is beginning to identify key principles of MHC and peptide recognition. The multicomponent assembly of the TCR complex illustrates general principles used by many receptors in the immune system, which rely on basic and acidic transmembrane residues to guide assembly. The intrinsic binding of the cytoplasmic domains of the CD31 and z chains to the inner leaflet of the plasma membrane represents a novel mechanism for control of receptor activation: Insertion of critical CD31 tyrosines into the hydrophobic membrane core prevents their phosphorylation before receptor engagement. LIGAND BINDING BY THE EXTRACELLULAR DOMAINS OF T-CELL RECEPTORS: STRUCTURAL BASIS OF ab AND gd TCR BINDING TO A DIVERSE GROUP OF LIGANDST he structures of many T-cellreceptors (TCRs) in their ligand-bound state have now been determined, allowing some of the general rules of antigen recognition to be distilled. Though the best studied interaction is the binding of abTCR with peptide-MHC complexes, it is highly instructive to compare the prototypical binding to peptide-MHC with the recognition of lipid antigen-CD1 complexes and engagement of nonclassical MHC class I molecules by gdTCRs. These comparisons show that the recognition strategies for these

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“…To elicit a sustained immune response, peptides need to form stable complexes with class I molecules (1,2), which means that they must conform to specific length and sequence requirements that were first identified by elution and sequencing, and then structurally understood by X-ray crystallography. Depending on the class I allotype, high-affinity peptides must be 8 to 10 aa long (such that the termini can form hydrogen bonding networks) and have defined side chains at particular positions that bind into specificity pockets at the bottom of the binding groove (3)(4)(5). This knowledge has been used to predict the binding affinity of any peptide sequence to a given class I allotype (6), and, together with theoretical simulations of the conformational movements of class I-peptide complexes, it has allowed the design of altered peptide ligands with higher binding affinities (7).…”

mentioning

confidence: 99%

Dipeptides promote folding and peptide binding of MHC class I molecules

Saini

Ostermeir

Ramnarayan

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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MHC class I molecules bind only those peptides with high affinity that conform to stringent length and sequence requirements. We have now investigated which peptides can aid the in vitro folding of class I molecules, and we find that the dipeptide glycyl-leucine efficiently supports the folding of HLA-A*02:01 and H-2K b into a peptide-receptive conformation that rapidly binds high-affinity peptides. Treatment of cells with glycyl-leucine induces accumulation of peptide-receptive H-2K b and HLA-A*02:01 at the surface of cells. Other dipeptides with a hydrophobic second amino acid show similar enhancement effects. Our data suggest that the dipeptides bind into the F pocket like the C-terminal amino acids of a highaffinity peptide.antigen presentation | ligand exchange | chemical chaperones | endoplasmic reticulum | quality control M HC class I molecules are transmembrane proteins that are vital to the mammalian antiviral and antitumor immune response. They bind intracellular peptides in the lumen of the endoplasmic reticulum (ER) to transport them to the cell surface for inspection by cytotoxic T lymphocytes. To elicit a sustained immune response, peptides need to form stable complexes with class I molecules (1, 2), which means that they must conform to specific length and sequence requirements that were first identified by elution and sequencing, and then structurally understood by X-ray crystallography. Depending on the class I allotype, high-affinity peptides must be 8 to 10 aa long (such that the termini can form hydrogen bonding networks) and have defined side chains at particular positions that bind into specificity pockets at the bottom of the binding groove (3-5). This knowledge has been used to predict the binding affinity of any peptide sequence to a given class I allotype (6), and, together with theoretical simulations of the conformational movements of class I-peptide complexes, it has allowed the design of altered peptide ligands with higher binding affinities (7). The high-affinity peptides thus identified can be used to fold many bacterially expressed denatured class I molecules into their native state (8). Consequently, high-affinity peptides have been called the "essential third subunit of MHC class I" (9).In living cells, class I molecules bind high-affinity peptides with the help of several chaperone proteins, collectively called the peptide loading complex (PLC). Importantly, experiments in vivo and in vitro have shown that, in the presence of the PLC, peptide loading is iterative, i.e., class I molecules first bind suboptimal peptides (peptides that are too long, too short, or do not have the requisite anchor residues) and gradually exchange them for higher-affinity ones (10, 11). The idea that class I molecules can initially fold with such suboptimal peptides is indeed supported by the crystal structures of several class I molecules with octamer or pentamer peptides (12, 13).In our effort to determine the minimum peptide requirements for the folding of class I, we have analyzed even smaller p...

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Antigenic peptide binding by class I and class II histocompatibility proteins

Abstract: The recent determination of the structure of a class II MHC molecule complexed to a specific peptide reveals both similarities and differences with peptide binding by class I MHC.

Cited by 291 publications

References 31 publications

Flexibility in MHC and TCR Recognition: Degenerate Specificity at the T Cell Level in the Recognition of Promiscuous Th Epitopes Exhibiting No Primary Sequence Homology

Flexibility in MHC and TCR Recognition: Degenerate Specificity at the T Cell Level in the Recognition of Promiscuous Th Epitopes Exhibiting No Primary Sequence Homology

Structural Biology of the T-cell Receptor: Insights into Receptor Assembly, Ligand Recognition, and Initiation of Signaling

Dipeptides promote folding and peptide binding of MHC class I molecules

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