scholarly journals ERp57 interacts with conserved cysteine residues in the MHC class I peptide-binding groove

FEBS Letters ◽  
2007 ◽  
Vol 581 (10) ◽  
pp. 1988-1992 ◽  
Author(s):  
Antony N. Antoniou ◽  
Susana G. Santos ◽  
Elaine C. Campbell ◽  
Sarah Lynch ◽  
Fernando A. Arosa ◽  
...  
Keyword(s):  
Mhc Class I ◽  
Peptide Binding ◽  
Class I ◽  
Cysteine Residues ◽  
Peptide Binding Groove ◽  
Binding Groove

scholarly journals The strength of selection is consistent across both domains of the MHC class I peptide-binding groove in birds

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Piotr Minias ◽  
Ke He ◽  
Peter O. Dunn
Keyword(s):  
Mhc Class I ◽  
Peptide Binding ◽  
Variable Region ◽  
Molecular Data ◽  
Class I ◽  
Amino Acid Polymorphism ◽  
Exon 2 ◽  
Peptide Binding Groove ◽  
Binding Groove ◽  
Avian Mhc

Abstract Background The Major Histocompatibility Complex (MHC) codes for the key vertebrate immune receptors responsible for pathogen recognition. Foreign antigens are recognized via their compatibility to hyper-variable region of the peptide-binding groove (PBR), which consists of two separate protein domains. Specifically, the PBR of the MHC class I receptors, which recognize intra-cellular pathogens, has two α domains encoded by exon 2 (α1) and exon 3 (α2) of the same gene. Most research on avian MHC class I polymorphism has traditionally focused exclusively on exon 3 and comparisons of selection between the two domains have been hampered by the scarcity of molecular data for exon 2. Thus, it is not clear whether the two domains vary in their specificity towards different antigens and whether they are subject to different selective pressure. Results Here, we took advantage of rapidly accumulating genomic resources to test for the differences in selection patterns between both MHC class I domains of the peptide-binding groove in birds. For this purpose, we compiled a dataset of MHC class I exon 2 and 3 sequences for 120 avian species from 46 families. Our phylogenetically-robust approach provided strong evidence for highly consistent levels of selection on the α1 and α2 domains. There were strong correlations in all selection measures (number of positively/negatively selected residues and dN/dS ratios) between both PBR exons. Similar positive associations were found for the level of amino acid polymorphism across the two domains. Conclusions We conclude that the strength of selection and the level of polymorphism are highly consistent between both peptide-binding domains (α1 and α2) of the avian MHC class I.

scholarly journals Mapping the peptide binding groove of MHC class I

2021 ◽  
Author(s):  
Janine-Denise Kopicki ◽  
Ankur Saikia ◽  
Stephan Niebling ◽  
Christian G&uumlnther ◽  
Maria M. Garcia-Alai ◽  
...  
Keyword(s):  
Binding Affinity ◽  
Mhc Class I ◽  
Peptide Binding ◽  
Essential Element ◽  
Native Mass Spectrometry ◽  
Class I ◽  
Peptide Antigens ◽  
Novel Approach ◽  
Peptide Binding Groove ◽  
Binding Groove

An essential element of adaptive immunity is the selective binding of peptide antigens by major histocompatibility complex (MHC) class I proteins and their presentation to cytotoxic T lymphocytes on the cell surface. Using native mass spectrometry, we here analyze the binding of peptides to an empty disulfide-stabilized HLA-A*02:01 molecule. This novel approach allows us to examine the binding properties of diverse peptides. The unique stability of our MHC class I even enables us to determine the binding affinity of complexes, which are suboptimally loaded with truncated or charge-reduced peptides. Notably, a unique erucamide adduct decouples affinity analysis from peptide identity alleviating issues usually attributed to clustering. We discovered that two anchor positions at the binding surface between MHC and peptide can be stabilized independently and further analyze the contribution of other peptidic amino acids on the binding. We propose this as an alternative, likely universally applicable method to artificial prediction tools to estimate the binding strength of peptides to MHC class I complexes quickly and efficiently. This newly described MHC class I-peptide binding affinity quantitation represents a much needed orthogonal, confirmatory approach to existing computational affinity predictions and has the potential to eliminate binding affinity biases and thus accelerate drug discovery in infectious diseases autoimmunity, vaccine design, and cancer immunotherapy.

scholarly journals The NK Cell MHC Class I Receptor Ly49A Detects Mutations on H-2Dd Inside and Outside of the Peptide Binding Groove

2001 ◽  
Vol 166 (7) ◽  
pp. 4422-4428 ◽  
Author(s):  
Naoki Matsumoto ◽  
Wayne M. Yokoyama ◽  
Somei Kojima ◽  
Kazuo Yamamoto
Keyword(s):  
Mhc Class I ◽  
Nk Cell ◽  
Peptide Binding ◽  
Class I ◽  
Peptide Binding Groove ◽  
Binding Groove

scholarly journals Structural Basis for the Restoration of TCR Recognition of an MHC Allelic Variant by Peptide Secondary Anchor Substitution

2004 ◽  
Vol 200 (11) ◽  
pp. 1445-1454 ◽  
Author(s):  
Michael J. Miley ◽  
Ilhem Messaoudi ◽  
Beatrix M. Metzner ◽  
Yudong Wu ◽  
Janko Nikolich-Žugich ◽  
...  
Keyword(s):  
T Cell ◽  
Mhc Class I ◽  
Peptide Binding ◽  
Cell Receptor ◽  
Class I ◽  
Structural Basis ◽  
Anchor Residue ◽  
Peptide Binding Groove ◽  
Binding Groove ◽  
Simplex Virus

Major histocompatibility complex (MHC) class I variants H-2Kb and H-2Kbm8 differ primarily in the B pocket of the peptide-binding groove, which serves to sequester the P2 secondary anchor residue. This polymorphism determines resistance to lethal herpes simplex virus (HSV-1) infection by modulating T cell responses to the immunodominant glycoprotein B498-505 epitope, HSV8. We studied the molecular basis of these effects and confirmed that T cell receptors raised against Kb–HSV8 cannot recognize H-2Kbm8–HSV8. However, substitution of SerP2 to GluP2 (peptide H2E) reversed T cell receptor (TCR) recognition; H-2Kbm8–H2E was recognized whereas H-2Kb–H2E was not. Insight into the structural basis of this discrimination was obtained by determining the crystal structures of all four MHC class I molecules in complex with bound peptide (pMHCs). Surprisingly, we find no concerted pMHC surface differences that can explain the differential TCR recognition. However, a correlation is apparent between the recognition data and the underlying peptide-binding groove chemistry of the B pocket, revealing that secondary anchor residues can profoundly affect TCR engagement through mechanisms distinct from the alteration of the resting state conformation of the pMHC surface.

scholarly journals Structural Definition of Duck Major Histocompatibility Complex Class I Molecules That Might Explain Efficient Cytotoxic T Lymphocyte Immunity to Influenza A Virus

2017 ◽  
Vol 91 (14) ◽  
Author(s):  
Yanan Wu ◽  
Junya Wang ◽  
Shuhua Fan ◽  
Rong Chen ◽  
Yanjie Liu ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Cytotoxic T Lymphocyte ◽  
Peptide Binding ◽  
Class I ◽  
Binding Motif ◽  
Mhc I ◽  
Peptide Binding Groove ◽  
Peptide Binding Motif ◽  
Binding Groove

ABSTRACT A single dominantly expressed allele of major histocompatibility complex class I (MHC I) may be responsible for the duck's high tolerance to highly pathogenic influenza A virus (HP-IAV) compared to the chicken's lower tolerance. In this study, the crystal structures of duck MHC I (Anpl-UAA*01) and duck β2-microglobulin (β2m) with two peptides from the H5N1 strains were determined. Two remarkable features were found to distinguish the Anpl-UAA*01 complex from other known MHC I structures. A disulfide bond formed by Cys95 and Cys112 and connecting the β5 and β6 sheets at the bottom of peptide binding groove (PBG) in Anpl-UAA*01 complex, which can enhance IAV peptide binding, was identified. Moreover, the interface area between duck MHC I and β2m was found to be larger than in other species. In addition, the two IAV peptides that display distinctive conformations in the PBG, B, and F pockets act as the primary anchor sites. Thirty-one IAV peptides were used to verify the peptide binding motif of Anpl-UAA*01, and the results confirmed that the peptide binding motif is similar to that of HLA-A*0201. Based on this motif, approximately 600 peptides from the IAV strains were partially verified as the candidate epitope peptides for Anpl-UAA*01, which is a far greater number than those for chicken BF2*2101 and BF2*0401 molecules. Extensive IAV peptide binding should allow for ducks with this Anpl-UAA*01 haplotype to resist IAV infection. IMPORTANCE Ducks are natural reservoirs of influenza A virus (IAV) and are more resistant to the IAV than chickens. Both ducks and chickens express only one dominant MHC I locus providing resistance to the virus. To investigate how MHC I provides IAV resistance, crystal structures of the dominantly expressed duck MHC class I (pAnpl-UAA*01) with two IAV peptides were determined. A disulfide bond was identified in the peptide binding groove that can facilitate Anpl-UAA*01 binding to IAV peptides. Anpl-UAA*01 has a much wider recognition spectrum of IAV epitope peptides than do chickens. The IAV peptides bound by Anpl-UAA*01 display distinctive conformations that can help induce an extensive cytotoxic T lymphocyte (CTL) response. In addition, the interface area between the duck MHC I and β2m is larger than in other species. These results indicate that HP-IAV resistance in ducks is due to extensive CTL responses induced by MHC I.

Peptide Binding to MHC Class I is Determined by Individual Pockets in the Binding Groove

1997 ◽  
Vol 46 (2) ◽  
pp. 137-146 ◽  
Author(s):  
T. E. JOHANSEN ◽  
K. McCULLOUGH ◽  
B. CATIPOVIC ◽  
X.‐M. SU ◽  
M. AMZEL ◽  
...  
Keyword(s):  
Mhc Class I ◽  
Peptide Binding ◽  
Class I ◽  
Binding Groove

scholarly journals Conformational differences in major histocompatibility complex-peptide complexes can result in alloreactivity.

1994 ◽  
Vol 179 (1) ◽  
pp. 213-219 ◽  
Author(s):  
S Chattopadhyay ◽  
M Theobald ◽  
J Biggs ◽  
L A Sherman
Keyword(s):  
Major Histocompatibility Complex ◽  
Peptide Binding ◽  
Class I ◽  
Major Histocompatibility ◽  
Wild Type ◽  
Mhc Molecules ◽  
Histocompatibility Complex ◽  
Type Molecule ◽  
Peptide Binding Groove ◽  
Binding Groove

Mutations within the class I major histocompatibility complex (MHC) molecule that affect a peptide binding can result in strong allogeneic responses. It is believed this reflects, in part, binding of a different set of endogenous peptides by each MHC molecule. We have examined the representation of allopeptides recognized by Kb-specific cytotoxic T lymphocytes (CTL) clones among targets that express either the Kb or the Kbm8 mutant. These class I molecules mutationally differ by several residues at the base of the peptide binding groove resulting in lack of recognition of bm8 targets by most Kb-specific CTL, and in strong mutual alloreactivity. Since these differences involve pockets in the base of the peptide binding groove that are presumed to contribute to the affinity of peptide binding, and there is evidence for differences in peptide binding by the mutant and wild type molecule, it was considered most likely that alloreactivity was due to binding of different sets of peptides by each of these molecules. Surprisingly, the allopeptides recognized by Kb-specific clones from a variety of responders, including bm8, are often found associated with both the wild type and mutant class I molecules. Although for some allopeptides the amount of peptide normally found associated with bm8 is less than that associated with Kb, reactivity could not be restored by increasing the amount of the relevant peptide. Thus, the basis for much of the alloreactivity observed in this particular mutant and wild type combination is not the presence or absence of the relevant allopeptide but rather the different conformation adapted by the peptide-MHC complex. These results allow us to conclude that strong alloreactive responses can result from T cell recognition of conformational differences between the stimulation and responder MHC molecules.

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