QSAR Study on MHC Class I A Alleles Based on the Novel Parameters of Amino Acids

2011 ◽  
Vol 18 (9) ◽  
pp. 956-963 ◽  
Author(s):  
Juan Wang ◽  
Xiao-Yu Wang ◽  
Mao Shu ◽  
Yuan-Qiang Wang ◽  
Yong Lin ◽  
...  
Keyword(s):  
Amino Acids ◽  
Mhc Class I ◽  
Class I ◽  
The Novel ◽  
Qsar Study

scholarly journals H-2M3a violates the paradigm for major histocompatibility complex class I peptide binding.

1995 ◽  
Vol 181 (5) ◽  
pp. 1817-1825 ◽  
Author(s):  
J M Vyas ◽  
J R Rodgers ◽  
R R Rich
Keyword(s):  
Amino Acids ◽  
Mhc Class I ◽  
Temperature Shift ◽  
Class I ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Compensatory Adaptation ◽  
Chemotactic Peptides ◽  
The Stability ◽  
Formyl Peptides

The major histocompatibility (MHC) class I-b molecule H-2M3a binds and presents N-formylated peptides to cytotoxic T lymphocytes. This requirement potentially places severe constraints on the number of peptides that M3a can present to the immune system. Consistent with this idea, the M3a-Ld MHC class I chimera is expressed at very low levels on the cell surface, but can be induced significantly by the addition of specific peptides at 27 degrees C. Using this assay, we show that M3a binds many very short N-formyl peptides, including N-formyl chemotactic peptides and canonical octapeptides. This observation is in sharp contrast to the paradigmatic size range of peptides of 8-10 amino acids binding to most class I-a molecules and the class I-b molecule Qa-2. Stabilization by fMLF-benzyl amide could be detected at peptide concentrations as low as 100 nM. While N-formyl peptides as short as two amino acids in length stabilized expression of M3a-Ld, increasing the length of these peptides added to the stability of peptide-MHC complexes as determined by 27-37 degrees C temperature shift experiments. We propose that relaxation of the length rule may represent a compensatory adaptation to maximize the number of peptides that can be presented by H-2M3a.

scholarly journals The viral set point in primary HIV infection is associated with specific amino acids in position 97 of MHC class I

Retrovirology ◽  
2012 ◽  
Vol 9 (S2) ◽  
Author(s):  
SA Vaidya ◽  
H Streeck ◽  
F Pereyra ◽  
ES Rosenberg ◽  
BD Walker ◽  
...  
Keyword(s):  
Amino Acids ◽  
Hiv Infection ◽  
Mhc Class I ◽  
Class I ◽  
Set Point ◽  
Primary Hiv Infection

scholarly journals Identification of a unique tumor antigen as rejection antigen by molecular cloning and gene transfer.

1986 ◽  
Vol 164 (5) ◽  
pp. 1516-1530 ◽  
Author(s):  
H J Stauss ◽  
C Van Waes ◽  
M A Fink ◽  
B Starr ◽  
H Schreiber
Keyword(s):  
Mhc Class I ◽  
Tumor Cell Line ◽  
Tumor Rejection ◽  
Class I ◽  
Transplantation Antigen ◽  
The Novel ◽  
Gene Encoding ◽  
Mhc Class I Molecule ◽  
T Cell Clone ◽  
I Gene

Tumor-specific transplantation antigens are antigens that can lead to complete immunological destruction of a transplanted cancer by the syngeneic host. When such antigens are expressed on cancers induced by chemical or physical carcinogens, then they are usually unique, i.e., antigenically different for each independently induced tumor. In this study, we show that the product of a gene encoding a novel MHC class I molecule and isolated from the murine UV light-induced regressor tumor 1591 represents one such unique tumor-specific transplantation antigen that causes tumor rejection. The major evidence comes from our finding that 1591 progressor variants regularly lost the gene encoding this antigen that is expressed in the parental tumor that regresses in normal mice; furthermore, reintroduction of this gene into a 1591 progressor variant by DNA transfection caused the progressor variant to regress in normal immunocompetent mice. Thus, the progressor tumor reverted to the parental regressor phenotype following transfection. Consistent with the conclusion that the expression of the novel MHC class I gene following transfection was responsible for the regressor phenotype is also our finding that a variant of the transfected tumor that had lost expression of the transfected gene resumed its progressive growth behavior. Finally, we show that the molecule encoded by the novel class I gene is specifically recognized by a syngeneic tumor-specific cytolytic T cell clone that we have previously shown to select in vitro for progressor variants from the parental regressor tumor cell line. It remains to be determined to what extent unique tumor-specific rejection antigens of other highly immunogenic regressor tumors are encoded by novel MHC class I genes and whether these genes represent germline mutations or somatic mutations caused by the carcinogen treatment.

scholarly journals An In-Depth Study of TCA cycles, OPA1, S6K1, ATPase, TLR4, MHC-class-I, GCs, and IFNs Bio-Synthesis, and Their Roles of Deficiency in Diabetes, Asthma, Cancer, etc and the NAD Roles in Their Activities

2021 ◽  
pp. 1-11
Author(s):  
Ashraf Marzouk El Tantawi ◽  
Keyword(s):  
Amino Acids ◽  
Mhc Class I ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Class I ◽  
Androgen Synthesis ◽  
Depth Study ◽  
Bio Synthesis

The roles of S6K1 is regulating ATPase, and GTPase synthesis, and consequently the endocytic proliferations including endocytic soluble MHC class II synthesis which regulate both SIRPα1 and TLR4 synthesis , where diabetes reflect deficiency in Ser amino acids that reflect deficiency in pyrimidines synthesis consequently deficiency in Estrogen and reflect increasing in androgen synthesis with increasing in consuming in purines (A&G) that lead to decreasing in anabolic processes which depends on presence of adenosine and guanosine stored in ribosimes.

scholarly journals The HLA A03 Supertype and Several Pan Species Major Histocompatibility Complex Class I A Allotypes Share a Preference for Binding Positively Charged Residues in the F Pocket: Implications for Controlling Retroviral Infections

2020 ◽  
Vol 94 (9) ◽  
Author(s):  
Natasja G. de Groot ◽  
Corrine M. C. Heijmans ◽  
Arnoud H. de Ru ◽  
Nel Otting ◽  
Frits Koning ◽  
...  
Keyword(s):  
Amino Acids ◽  
Mhc Class I ◽  
Peptide Binding ◽  
Class I ◽  
Content Type ◽  
Basic Amino Acids ◽  
Immunodeficiency Virus ◽  
Retroviral Infections ◽  
Free Ranging ◽  
Hiv 1

ABSTRACT The major histocompatibility complex (MHC) class I region of humans, chimpanzees (Pan troglodytes), and bonobos (Pan paniscus) is highly similar, and orthologues of HLA-A, -B, and -C are present in both Pan species. Based on functional characteristics, the different HLA-A allotypes are classified into different supertypes. One of them, the HLA A03 supertype, is widely distributed among different human populations. All contemporary known chimpanzee and bonobo MHC class I A allotypes cluster genetically into one of the six HLA-A families, the HLA-A1/A3/A11/A30 family. We report here that the peptide-binding motif of the Patr-A*05:01 allotype, which is commonly present in a cohort of western African chimpanzees, has a strong preference for binding peptides with basic amino acids at the carboxyl terminus. This phenomenon is shared with the family members of the HLA A03 supertype. Based on the chemical similarities in the peptide-binding pocket, we inferred that the preference for binding peptides with basic amino acids at the carboxyl terminus is widely present among the human, chimpanzee, and bonobo MHC-A allotypes. Subsequent in silico peptide-binding predictions illustrated that these allotypes have the capacity to target conserved parts of the proteome of human immunodeficiency virus type 1 (HIV-1) and the simian immunodeficiency virus SIVcpz. IMPORTANCE Most experimentally infected chimpanzees seem to control an HIV-1 infection and are therefore considered to be relatively resistant to developing AIDS. Contemporary free-ranging chimpanzees may carry SIVcpz, and there is evidence for AIDS-like symptoms in these free-ranging animals, whereas SIV infections in bonobos appear to be absent. In humans, the natural control of an HIV-1 infection is strongly associated with the presence of particular HLA class I allotypes. The ancestor of the contemporary living chimpanzees and bonobos survived a selective sweep targeting the MHC class I repertoire. We have put forward a hypothesis that this may have been caused by an ancestral retroviral infection similar to SIVcpz. Characterization of the relevant MHC allotypes may contribute to understanding the shaping of their immune repertoire. The abundant presence of MHC-A allotypes that prefer peptides with basic amino acids at the C termini suggests that these molecules may contribute to the control of retroviral infections in humans, chimpanzees, and bonobos.

scholarly journals Conserved Amino Acids within the Adenovirus 2 E3/19K Protein Differentially Affect Downregulation of MHC Class I and MICA/B Proteins

2009 ◽  
Vol 184 (1) ◽  
pp. 255-267 ◽  
Author(s):  
Martina Sester ◽  
Katja Koebernick ◽  
Douglas Owen ◽  
Minghui Ao ◽  
Yana Bromberg ◽  
...  
Keyword(s):  
Amino Acids ◽  
Mhc Class I ◽  
Class I ◽  
Conserved Amino Acids

scholarly journals Evaluation of machine learning methods to predict peptide binding to MHC Class I proteins

2017 ◽  
Author(s):  
Rohit Bhattacharya ◽  
Ashok Sivakumar ◽  
Collin Tokheim ◽  
Violeta Beleva Guthrie ◽  
Valsamo Anagnostou ◽  
...  
Keyword(s):  
Neural Network ◽  
Machine Learning ◽  
Amino Acids ◽  
Mhc Class I ◽  
Mhc Class Ii ◽  
Class I ◽  
Learning Methods ◽  
Machine Learning Methods ◽  
Histocompatibility Complex ◽  
Mhc Alleles

AbstractBinding of peptides to Major Histocompatibility Complex (MHC) proteins is a critical step in immune response. Peptides bound to MHCs are recognized by CD8+ (MHC Class I) and CD4+ (MHC Class II) T-cells. Successful prediction of which peptides will bind to specific MHC alleles would benefit many cancer immunotherapy appications. Currently, supervised machine learning is the leading computational approach to predict peptide-MHC binding, and a number of methods, trained using results of binding assays, have been published. Many clinical researchers are dissatisfied with the sensitivity and specificity of currently available methods and the limited number of alleles for which they can be applied. We evaluated several recent methods to predict peptide-MHC Class I binding affinities and a new method of our own design (MHCnuggets). We used a high-quality benchmark set of 51 alleles, which has been applied previously. The neural network methods NetMHC, NetMHCpan, MHCflurry, and MHCnuggets achieved similar best-in-class prediction performance in our testing, and of these methods MHCnuggets was significantly faster. MHCnuggets is a gated recurrent neural network, and the only method to our knowledge which can handle peptides of any length, without artificial lengthening and shortening. Seventeen alleles were problematic for all tested methods. Prediction difficulties could be explained by deficiencies in the training and testing examples in the benchmark, suggesting that biological differences in allele-specific binding properties are not as important as previously claimed. Advances in accuracy and speed of computational methods to predict peptide-MHC affinity are urgently needed. These methods will be at the core of pipelines to identify patients who will benefit from immunotherapy, based on tumor-derived somatic mutations. Machine learning methods, such as MHCnuggets, which efficiently handle peptides of any length will be increasingly important for the challenges of predicting immunogenic response for MHC Class II alleles.Author SummaryMachine learning methods are a popular approach for predicting whether a peptide will bind to Major Histocompatibility Complex (MHC) proteins, a critical step in activation of cytotoxic T-cells. The input to these methods is a peptide sequence and an MHC allele of interest, and the output is the predicted binding affinity. MHC Class I and II proteins bind peptides of 8-11 amino acids and 16-26 amino acids respectively. This has been an obstacle for machine learning, because the methods used to date can only handle fixed-length inputs. We show that a recently developed technique known as gated recurrent neural networks can handle peptides of variable length and predict peptide-MHC binding as well or better than existing methods, at substantially faster speeds. Our results have implications for the hundreds of MHC alleles that cannot be predicted with current methods.

scholarly journals The requirement for proteasome activity class I major histocompatibility complex antigen presentation is dictated by the length of preprocessed antigen.

1996 ◽  
Vol 183 (4) ◽  
pp. 1545-1552 ◽  
Author(s):  
B Yang ◽  
Y S Hahn ◽  
C S Hahn ◽  
T J Braciale
Keyword(s):  
Amino Acids ◽  
Major Histocompatibility Complex ◽  
Antigen Presentation ◽  
Mhc Class I ◽  
Proteasome Activity ◽  
Class I ◽  
Target Cells ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Mhc Class I Molecules

Accumulating evidence has implicated the proteasome in the processing of protein along the major histocompatibility complex (MHC) class I presentation pathway. The availability of potent proteasome inhibitors provides an opportunity to examine the role of proteasome function in antigen presentation by MHC class I molecules to CD8+ cytotoxic T lymphocytes (CTLs). We have investigated the processing and presenting of antigenic epitopes from influenza hemagglutinin in target cells treated with the inhibitor of proteasome activity MG132. In the absence of proteasome activity, the processing and presentation of the full-length hemagglutinin was abolished, suggesting the requirement for proteasome function in the processing and presentation of the hemagglutinin glycoprotein. Epitope-containing translation products as short as 21 amino acids when expressed in target cells required proteasome activity for processing and presentation of the hemagglutin epitope to CTLs. However, when endogenous peptides of 17 amino acids or shorter were expressed in target cells, the processing and presentation of epitopes contained in these peptides were insensitive to the proteasome inhibitor. Our results support the hypothesis that proteasome activity is required for the generation of peptides presented by MHC class I molecules and that the requirement for proteasome activity is dependent on the size of the translation product expressed in the target cell. The implications of these findings are discussed.

The Study of Specificities of Interaction between Peptides and MHC Molecules

2010 ◽  
Vol 143-144 ◽  
pp. 1254-1258 ◽  
Author(s):  
Tao Liu ◽  
Zhan Xin Zhang ◽  
Huan Wei ◽  
Hong Kui Hu ◽  
Feng Ming Wang
Keyword(s):  
Amino Acids ◽  
Mhc Class I ◽  
Class I ◽  
Support Vector ◽  
Binding Affinities ◽  
Mhc Molecules ◽  
Mhc Class I Molecule ◽  
Antigen Peptide ◽  
Amino Acid Descriptors ◽  
Epitope Vaccines

Determining which peptides bind to a specific major histocompatibility complex (MHC) class I molecule is not only helpful to understand the mechanism of immunity, but also to develop effective anti-tumor epitope vaccines. In order to further study the specificity of MHC class I molecule binding antigen peptide, the support vector regression (SVR) and four amino acid descriptors were used to build four models of predicting binding affinities between peptides and MHC class I molecules. Comparison among performances of the four models indicated that the model based on physicochemical properties of amino acids is more satisfying (AC=75.0%, CC=0.499). Furthermore, the specificities of MHC class I molecule binding antigen peptide were obtained through analysis based on the contribution of the amino acids to peptide-MHC class I molecule binding affinities in the predictive model.

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