scholarly journals Structural features for peptides binding the class I molecules

2001 ◽  
Vol 3 (S1) ◽  
Author(s):  
I McKenzie ◽  
V Apostolopoulos ◽  
Y Mu ◽  
IA Wilson
Keyword(s):  
Structural Features ◽  
Class I

scholarly journals Variations in MHC class I antigen presentation and immunopeptidome selection pathways

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 1177
Author(s):  
Anita J. Zaitouna ◽  
Amanpreet Kaur ◽  
Malini Raghavan
Keyword(s):  
Cell Surface ◽  
Antigen Presentation ◽  
Surface Expression ◽  
Structural Features ◽  
Class I ◽  
Cell Surface Expression ◽  
Immune Recognition ◽  
Antigen Receptors ◽  
Class I Mhc ◽  
Mhc I

Major histocompatibility class I (MHC-I) proteins mediate immunosurveillance against pathogens and cancers by presenting antigenic or mutated peptides to antigen receptors of CD8+ T cells and by engaging receptors of natural killer (NK) cells. In humans, MHC-I molecules are highly polymorphic. MHC-I variations permit the display of thousands of distinct peptides at the cell surface. Recent mass spectrometric studies have revealed unique and shared characteristics of the peptidomes of individual MHC-I variants. The cell surface expression of MHC-I–peptide complexes requires the functions of many intracellular assembly factors, including the transporter associated with antigen presentation (TAP), tapasin, calreticulin, ERp57, TAP-binding protein related (TAPBPR), endoplasmic reticulum aminopeptidases (ERAPs), and the proteasomes. Recent studies provide important insights into the structural features of these factors that govern MHC-I assembly as well as the mechanisms underlying peptide exchange. Conformational sensing of MHC-I molecules mediates the quality control of intracellular MHC-I assembly and contributes to immune recognition by CD8 at the cell surface. Recent studies also show that several MHC-I variants can follow unconventional assembly routes to the cell surface, conferring selective immune advantages that can be exploited for immunotherapy.

scholarly journals H-2Kd-restricted antigenic peptides share a simple binding motif.

1991 ◽  
Vol 174 (3) ◽  
pp. 603-612 ◽  
Author(s):  
P Romero ◽  
G Corradin ◽  
I F Luescher ◽  
J L Maryanski
Keyword(s):  
Amino Acid ◽  
Mhc Class I ◽  
Specific Binding ◽  
Structural Features ◽  
Class I ◽  
Binding Motif ◽  
Antigenic Peptides ◽  
Amino Acid Residues ◽  
Antigenic Activity ◽  
Mhc Class I Molecule

We have defined structural features that are apparently important for the binding of four different, unrelated antigenic epitopes to the same major histocompatibility complex (MHC) class I molecule, H-2Kd. The four epitopes are recognized in the form of synthetic peptides by cytotoxic T lymphocytes of the appropriate specificity. By analysis of the relative potency of truncated peptides, we demonstrated that for each of the four epitopes, optimal antigenic activity was present in a peptide of 9 or 10 amino acid residues. A comparison of the relative competitor activity of the different-length peptides in a functional competition assay, as well as in a direct binding assay based on photoaffinity labeling of the Kd molecule, indicated that the enhanced potency of the peptides upon reduction in length was most likely due to a higher affinity of the shorter peptides for the Kd molecule. A remarkably simple motif that appears to be important for the specific binding of Kd-restricted peptides was identified by the analysis of peptides containing amino acid substitutions or deletions. The motif consists of two elements, a Tyr in the second position relative to the NH2 terminus and a hydrophobic residue with a large aliphatic side chain (Leu, Ile, or Val) at the COOH-terminal end of the optimal 9- or 10-mer peptides. We demonstrated that a simple peptide analogue (AYP6L) that incorporates the motif can effectively and specifically interact with the Kd molecule. Moreover, all of the additional Kd-restricted epitopes defined thus far in the literature contain the motif, and it may thus be useful for the prediction of new epitopes recognized by T cells in the context of this MHC class I molecule.

scholarly journals Potential Immunocompetence of Proteolytic Fragments Produced by Proteasomes before Evolution of the Vertebrate Immune System

1997 ◽  
Vol 186 (2) ◽  
pp. 209-220 ◽  
Author(s):  
Gabriele Niedermann ◽  
Rudolf Grimm ◽  
Elke Geier ◽  
Martina Maurer ◽  
Claudio Realini ◽  
...  
Keyword(s):  
Immune System ◽  
Mhc Class I ◽  
Structural Features ◽  
Interferon Γ ◽  
Class I ◽  
Direct Products ◽  
Vertebrate Immune System ◽  
Mhc Class I Molecules

To generate peptides for presentation by major histocompatibility complex (MHC) class I molecules to T lymphocytes, the immune system of vertebrates has recruited the proteasomes, phylogenetically ancient multicatalytic high molecular weight endoproteases. We have previously shown that many of the proteolytic fragments generated by vertebrate proteasomes have structural features in common with peptides eluted from MHC class I molecules, suggesting that many MHC class I ligands are direct products of proteasomal proteolysis. Here, we report that the processing of polypeptides by proteasomes is conserved in evolution, not only among vertebrate species, but including invertebrate eukaryotes such as insects and yeast. Unexpectedly, we found that several high copy ligands of MHC class I molecules, in particular, self-ligands, are major products in digests of source polypeptides by invertebrate proteasomes. Moreover, many major dual cleavage peptides produced by invertebrate proteasomes have the length and the NH2 and COOH termini preferred by MHC class I. Thus, the ability of proteasomes to generate potentially immunocompetent peptides evolved well before the vertebrate immune system. We demonstrate with polypeptide substrates that interferon γ induction in vivo or addition of recombinant proteasome activator 28α in vitro alters proteasomal proteolysis in such a way that the generation of peptides with the structural features of MHC class I ligands is optimized. However, these changes are quantitative and do not confer qualitatively novel characteristics to proteasomal proteolysis. The data suggest that proteasomes may have influenced the evolution of MHC class I molecules.

scholarly journals Species-restricted interactions between CD8 and the alpha 3 domain of class I influence the magnitude of the xenogeneic response.

1989 ◽  
Vol 170 (4) ◽  
pp. 1091-1101 ◽  
Author(s):  
M J Irwin ◽  
W R Heath ◽  
L A Sherman
Keyword(s):  
T Cells ◽  
Cell Lines ◽  
Human Cell ◽  
Structural Features ◽  
T Cell Response ◽  
Class I ◽  
Mhc Molecules ◽  
Specific Manner ◽  
Species Specific

As compared with the vigorous T cell response normally observed against allogeneic MHC molecules, T cells recognize xenogeneic MHC molecules poorly. To define structural features of the MHC molecule important for such species-specific recognition, HLA-A2(A2)-specific murine CTL were examined for their recognition of transfected cell lines expressing the class I molecules A2 or A2/H-2Kb(A2/Kb). A2/Kb is a chimeric molecule consisting of the alpha 1 and alpha 2 domains of A2 and the alpha 3, transmembrane, and cytoplasmic regions of Kb. The majority of CTL clones showed enhanced recognition of transfected cell lines expressing this chimeric molecule. Enhanced recognition was shown to correlate with sensitivity of the CTL clones to inhibition by anti-CD8 antibody. These results suggested that CD8 may interact with class I in a species-specific manner, and that suboptimal CD8 interaction with the alpha 3 domain of xenogeneic molecules may be an important contribution to poor xenoreactivity. This conclusion was supported by the capacity of A2/Kb, but not A2 human cell transfectants, to induce a primary in vitro CTL xenoresponse specific for A2.

scholarly journals Synthetic signals for ubiquitin-dependent proteolysis.

1995 ◽  
Vol 15 (8) ◽  
pp. 4086-4094 ◽  
Author(s):  
S Sadis ◽  
C Atienza ◽  
D Finley
Keyword(s):  
Alpha Helix ◽  
Class Ii ◽  
Structural Features ◽  
Proteolytic Processing ◽  
Class I ◽  
Class Iii ◽  
Reporter Protein ◽  
Hydrophobic Residues ◽  
Sequence Elements ◽  
Beta Galactosidase

Short-lived proteins are targeted for turnover by sequence elements known as degradation signals. Because of the large size and heterogeneity of these signals, the structural features important for their function are not well defined. In this study, we have isolated three classes of degradation signals by screening short artificial sequences for the ability to destabilize a reporter protein. Class I and class II signals were derived by inserting random nonapeptide sequences after the second residue of beta-galactosidase. Class III signals contained five-residue homopolymers at the same position. Class I beta-galactosidase turnover was inhibited in mutants lacking either the ubiquitin-conjugating enzyme Ubc2 or the ubiquitin protein ligase Ubr1. Class I random inserts functioned to promote N-terminal proteolytic processing and define a novel pathway for exposure of residues that are destabilizing according to the N-end rule. Efficient degradation of proteins containing class II signals required at least three Ubc enzymes: Ubc6, Ubc7, and either one of the related enzymes Ubc4 and Ubc5. Analysis of 56 amino acid substitutions in the class II signal suggested that it is recognized in the form of an amphipathic alpha helix. Class III signals consisted of short tracts of hydrophobic residues such as Leu and Ile. Degradation of class III proteins involved the Ubc4 and Ubc5 enzymes but not Ubc2, Ubc6, or Ubc7. Clusters of hydrophobic residues appear to be critical for the recognition of both class II and class III signals.

Identification and characterisation of a novel class I endo-β-1,3-glucanase regulated by salicylic acid, ethylene and fungal pathogens in strawberry

2012 ◽  
Vol 39 (5) ◽  
pp. 412 ◽  
Author(s):  
Martín G. Martínez Zamora ◽  
Carlos Grellet Bournonville ◽  
Atilio P. Castagnaro ◽  
Juan C. Díaz Ricci
Keyword(s):  
Salicylic Acid ◽  
Fungal Pathogens ◽  
Plant Defence ◽  
Structural Features ◽  
Class I ◽  
Colletotrichum Acutatum ◽  
Fragaria Ananassa ◽  
Biotic And Abiotic Stress ◽  
High Degree ◽  
Avirulent Isolate

The identification of a full length cDNA encoding an endo-β-1,3-glucanase (FaOGBG-5) from strawberry (Fragaria × ananassa Duch) is reported. The analysis of the deduced amino acid sequence of FaOGBG-5 showed that it shares typical structural features and a high degree of identity with other plant β-1,3-glucanases of the class I. The expression of FaOGBG-5 in plants infected with a virulent isolate of Colletotrichum acutatum and an avirulent isolate of Colletotrichum fragariae was examined. Induction of expression was observed with both pathogens but exhibited a delayed high expression with the virulent one. Additionally, the accumulation of FaOGBG-5 transcripts was also observed after treatments with the stress related hormones salicylic acid and ethylene. Results obtained suggest that the β-1,3-glucanase encoded by FaOGBG-5 may be implicated in plant defence against biotic and abiotic stress.

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