Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “antigenic peptide”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed2024

Targeting peptide antigens using a multiallelic MHC I-binding system.

Identifying highly specific T cell receptors (TCRs) or antibodies against epitopic peptides presented by class I major histocompatibility complex (MHC I) proteins remains a bottleneck in the development of targeted therapeutics. Here, we introduce targeted recognition of antigen-MHC complex reporter for MHC I (TRACeR-I), a generalizable platform for targeting peptides on polymorphic HLA-A*, HLA-B* and HLA-C* allotypes while overcoming the cross-reactivity challenges of TCRs. Our TRACeR-MHC I co-crystal structure reveals a unique antigen recognition mechanism, with TRACeR forming extensive contacts across the entire peptide length to confer single-residue specificity at the accessible positions. We demonstrate rapid screening of TRACeR-I against a panel of disease-relevant HLAs with peptides derived from human viruses (human immunodeficiency virus, Epstein-Barr virus and severe acute respiratory syndrome coronavirus 2), and oncoproteins (Kirsten rat sarcoma virus, paired-like homeobox 2b and New York esophageal squamous cell carcinoma 1). TRACeR-based bispecific T cell engagers and chimeric antigen receptor T cells exhibit on-target killing of tumor cells with high efficacy in the low nanomolar range. Our platform empowers the development of broadly applicable MHC I-targeting molecules for research, diagnostic and therapeutic applications.

Humans↗
PubMed1979

Lymphocyte specificity to protein antigens. II. Fine specificity of T-cell activation with cytochrome c and derived peptides as antigenic probes.

Murine T-lymphocyte specificity was determined in a system of antigen driven in vitro T-cell proliferation using cytochrome c molecules from different species, their derived peptides and reconstituted hybrid proteins. It was observed that primed T cells could discriminate between peptide fragments which differed from each other at a single amino acid residue. These conclusions were substantiated by the pattern of cross-reactivity noted in the response of closely related cytochrome c proteins as well as when artificial hybrid molecules reconstituted by the covalent linkage of peptide fragments were analyzed. The pattern of specificity observed appeared to be haplotype (BDF1) dependent although similar conclusions about the fine specificity of T cells in the response to cytochrome c have been obtained in other strains but associated with different residues.

Amino Acid Sequence↗
PubMed2024

Innovations Toward Immunopeptidomics.

Over the past 30 years, immunopeptidomics has grown alongside improvements in mass spectrometry technology, genomics, transcriptomics, T cell receptor sequencing, and immunological assays to identify and characterize the targets of activated T cells. Together, multiple research groups with expertise in immunology, biochemistry, chemistry, and peptide mass spectrometry have come together to enable the isolation and sequence identification of endogenous major histocompatibility complex (MHC)-bound peptides. The idea to apply highly sensitive mass spectrometry techniques to study the landscape of peptide antigens presented by cell surface MHCs was innovative and continues to be successfully used and improved upon to deepen our understanding of how peptide antigens are processed and presented to T cells. Multiple research groups were involved in this bringing immunopeptidomics to the forefront of translational research, and we will highlight the contributions of one of the earliest developers, Professor Donald F. Hunt, and his research group at the University of Virginia. The Hunt laboratory applied cutting edge mass spectroscopy-based immunopeptidomics to study cancer, autoimmunity, transplant rejection, and infectious diseases. Across these diverse research areas, the Hunt laboratory and collaborators would characterize previously unknown MHC peptide-binding motifs and identify immunologically active antigens using ultra sensitive mass spectrometry techniques. Amazingly, many of the MHC-bound peptide antigens discovered in collaborations with the Hunt laboratory were sequenced by mass spectrometry before the completion of the human genome using manual de novo sequencing. In this perspective article, we will chronicle the work of the Hunt laboratory and their many collaborators that would be a major part of the foundation for mass spectrometry-based immunopeptidomics and its application to immunology research.

Animals↗
PubMed1978

The detection of "purified" incubation damage by several radioimmunoassay separation methods.

Damage to labeled peptides has been recognized as an almost unavoidable consequence of exposure to plasma during radioimmunoassay incubat ions, which can cause serious errors in estimating plasma hormone concentrations. Surprisingly little is known about the nature and behavior of damaged labeled peptides in various systems for separating antibody-bound from free labeled hormones. This is due in part to lack of a generally applicable definition of "incubation damage" as an altered molecule rather than a phenomenon observed in the separation system. We have proposed the definition, "nonimmunoreactive radioactive peptide(s) produced during incubation of radioactively labeled peptide antigens." With 125I-hbetaMSH used as a model labeled peptide antigen, incubation damage was produced under defined conditions and purified by gel filtration. It appeared smaller than 125I-hbetaMSH, suggesting that it resulted from enzymic proteolysis. The behavior of purified incubation damage in five representative separation systems was not consistently predictable. In the paper chromatoelectrophoresis and QUSO-plasma systems, it behaved like a large molecule, partitioning in the "bound" phase. In these two systems, incubation damage must be detected in appropriate control tubes containing the specimen without antibody. In the dextran-charcoal, polyethylene glycol, and second-antibody systems, damage behaved like a small nonimmunoreactive peptide and partitioned in the "free" phase. In these systems, since incubation damage cannot be separated from free 125I-labeled peptide, damage control tubes must have excess antibody added after incubation. The apparent lack of incubation damage in some radioimmunoassays may be due to inappropriate controls for its detection, leading to erroneous estimation of plasma hormone concentrations.

Charcoal↗
PubMed1979

Antigenic drift in type A influenza virus: peptide mapping and antigenic analysis of A/PR/8/34 (HON1) variants selected with monoclonal antibodies.

Variants of A/PR/8/34 (HON1) influenza virus, having hemagglutinin molecules with probably a single altered antigenic determinant, were isolated by growing the virus in the presence of the monoclonal hybridoma antibody PEG-1. The variants were analyzed by peptide mapping and characterized antigenically by using PEG-1 and four other monoclonal hybridoma antibodies to PR8 hemagglutinin. Peptide maps of the large hemagglutinin polypeptide, HA1, from 8 out of 10 variants showed a single changed peptide. This peptide from two of the variants was analyzed, and in each case a serine residue in the wild-type hemagglutinin was replaced by leucine in the variant. Although these eight variants showed identical peptide maps, one could be discriminated antigenically from the others with one of the hybridomas. (The peptide maps represented about one-third of the HA1 molecule.) Of the other two variants, one gave the same HA1 map as the wild type, but could be distinguished antigenically from wild-type virus by two of the hybridomas. The other was unique, and could be distinguished, both antigenically and by peptide mapping, from the other variants. Since a large number of the variants selected with PEG-1 showed the same peptide change, it is likely that this alteration in amino acid sequence (serine to leucine) was responsible for the inability of the variants to bind PEG-1 monoclonal antibody. We do not know, however, whether the changed amino acids were located within the antigenic sites or whether the change occurred somewhere else in the hemagglutinin molecule and altered the determinants through conformational changes.

Amino Acids↗
PubMed1977

Colonic tumor membrane-associated glycoprotein: isolation of antigenically-active peptides after chemical cleavage.

A membrane-associated glycoprotein fraction, referred to a CEA-M was isolated from human colonic tumor tissue by sodium dodecyl sulfate extraction of membrane fragments followed by wheat germ agglutinin affinity chromatography, Bio-Gel A-1.5 gel filtration and preparative slab gel electrophoresis. With a m.w. of approximately 200,000, isoelectric point of about 4.2 and carbohydrate:protein ratio of 2:1, this glycoprotein has physiocochemical and antigenic similarities to carcinoembryonic antigen, CEA. Immunochemical studies have shown that antiserum developed for this glycoprotein possesses relative specificity for human colonic carcinomas. Chemical cleavage of this glycoprotein by 2-nitro-5-thiocyanobenzoic acid resulted in three major Coomassie Blue and two periodic acid Schiff stainable fragments (one of which stains with both). It was found that one of the glycopeptides, labeled as TA, isolated by affinity and covalent chromatography, contained 77% carbohydrates and possessed antigenic determinants recognized by at least 70% of the antibody population raised against the total glycoprotein fraction; purified antibodies to this region of the molecule seem promising for the development of a specific assay for gastrointestinal tumors.

Antibodies, Neoplasm↗
PubMed1977

Induction of neutralizing antibodies and immunity in vaccinated guinea pigs by cyanogen bromide-peptides of VP3 of foot-and-mouth disease virus.

The specificity of guinea pig antisera against large cyanogen bromide-cleaved peptides of the virus capsid protein VP3 of foot-and-mouth disease virus type O1, strain Kaufbeuren has been characterized by double immunodiffusion, virus neutralization and protection tests. Antibodies to purified 146S particles and the cleavage peptides of VP3 showed an incomplete cross-section against VP3 peptide antigen when reacted in immunodiffusion tests, indicating that new antigenic determinants are exhibited by the peptides which are not recognized by the antiserum against the native virus proteins. The immune response against the reduced, unfolded chain constituents of VP3 was lower in comparison to that of native virus particles but still some immunological determinants remained actively capable of inducing virus-neutralizing antibodies in immunized guinea pigs.

Animals↗
PubMed1975

Immunochemical studies on the human pathogen Sporothrix schenckii: effects of chemical and enzymatic modification of the antigenic compounds upon immediate and delayed reactions.

The rhamnose-containing polysaccharide-peptide compound derived from the cells of the pathogenic fungus Sporothrix schenckii has been shown to contain 87.1% carbohydrate and 12.5% peptide and to give rise to both immediate- and delayed-type reactions in sensitized guinea pigs. The capacity to induce immediate-type reaction, passive cutaneous anaphylaxis, was completely lost by degradation of the carbohydrate moiety by periodate, whereas the ability to induce the delayed-type reactions of migration inhibition (in vitro) and the sporotrichin reaction (in vivo) were only slightly affected by periodate treatment. On the other hand, delayed "reactivities" to the compound were considerably reduced by treatment with papain, whereas the immediate-type reaction remained positive. These results lead to a conclusion that the rhamnose-containing polysaccharide of the polysaccharide-peptide antigenic compound plays an important role in the immediate-type reaction, whereas the peptide is largely responsible for the delayed-type reaction.

Amino Acids↗
PubMed2026

Cancer Immune Responsiveness and MHC Class I Antigen Presentation: Mechanisms of Immune Escape and Immunotherapy Resistance in Gastrointestinal Cancers.

The Antigen Processing and Presentation Machinery (APM) is essential for immune surveillance by enabling the presentation of antigenic peptides to T lymphocytes and facilitating the elimination of infected or transformed cells. In cancer, the integrity of this process influences cancer immune responsiveness (CIR), defined as a tumour's capacity to be recognised by the immune system and respond to immunotherapy. Tumours with intact antigen presentation pathways are more likely to generate effective antitumour responses, whereas APM defects promote immune escape and therapeutic resistance. Cancer cells frequently evade immune detection through altered antigen processing or reduced expression of major histocompatibility complex (MHC) class I molecules, limiting tumour antigen presentation to cytotoxic T lymphocytes. These alterations are increasingly recognised as determinants of response to immune checkpoint inhibitors and potential predictive biomarkers. APM defects may be reversible or irreversible. Interferon-mediated signalling can restore MHC class I expression and T-cell cytotoxicity in some tumours, whereas permanent genomic alterations affecting human leukocyte antigen (HLA) class I genes, β2-microglobulin (β2-m), or interferon-γ (IFN-γ) pathway components can severely impair antigen presentation. Emerging evidence highlights four mechanistic levels of APM perturbation: peptide generation, peptide loading, MHC class I integrity, and epigenetic regulation. Each contributes to distinct patterns of immune evasion. This review examines how MHC class I alterations influence CIR and contribute to immune evasion and immunotherapy resistance in gastrointestinal malignancies, while discussing therapeutic strategies to restore or bypass APM deficiencies.

Humans↗
PubMed1979

Change in specificity of antibodies to a random synthetic branched polypeptide in mice tolerant to its ordered analogs.

The crossreactivity between the random synthetic polypeptide antigen, (Tyr,Glu)-poly(DLAla)- -poly(Lys), and its ordered sequence analogs, (Tyr-Tyr-Glu-Glu)-poly(DLAla)- -poly(Lys) and (Tyr-Glu-Tyr-Glu)-poly(DLAla)- -poly(Lys), has been studied on the level of tolerance induction. Induction of tolerance to the random (Tyr,Glu)-poly(DLAla)- -poly(Lys) affected the response of the tolerant mice to the homologous antigen as well as to (Tyr-Tyr-Glu-Glu)-poly(DLAla)- -poly(Lys), which was shown previously to represent the major determinant of (Tyr,Glu)-poly(DLAla)- -poly(Lys). In contrast, these mice responded with high antibody titers to the hardly crossreacting (Tyr-Glu-Tyr-Glu)-poly(DLAla)- -poly(Lys). Mice tolerant to the ordered peptide antigen (Tyr-Glu-Tyr-Glu)-poly(DLAla)- -poly(Lys) did not respond to the homologous polypeptide; however, their immune response to either (Tyr-Glu)-poly(DLAla)- -poly(Lys) or (Tyr-Tyr-Glu-Glu)-poly(DLAla)- -poly(Lys) was not affected. Mice that were tolerant to (Tyr-Tyr-Glu-Glu)-poly(DLAla)- -poly(Lys) responded well to (Tyr-Glu-Tyr-Glu)-poly(DLAla)- -poly(Lys). Furthermore, these mice produced high antibody titers after immunization with the random (Tyr,Glu)-poly(DLAla)- -poly(Lys). However, the antibodies produced were not specific to the major determinant of (Tyr,Glu)-poly(DLAla)- -poly(Lys), namely, Tyr-Tyr-Glu-Glu, but were directed to minor determinants of the random polypeptide, including Tyr-Glu-Tyr-Glu, which are not immunopotent when nontolerant mice are immunized with (Tyr,Glu)-poly(DLAla)- -poly(Lys). Thus, whereas antigenic specificity reflects itself also at the level of tolerance induction, the animals that had been made tolerant are capable of responding to previously silent antigenic determinants.

Animals↗
PubMed1975

The continuing challenge of gallbladder cancer. Survey of thirty years' experience at the University of Chicago.

The current concepts of the etiologic factors and spread of carcinoma of the gallbladder are discussed. The experience at the university of Chicago with this condition over a period of thirty years is reviewed. Of eighty-two cases diagnosed during this time, 88 per cent of the patients died within one year of diagnosis and the five year survival rate was 5 per cent. The difficulties in diagnosis of cholecystic neoplasms are considered, and the possibility of increasing diagnostic accuracy by the use of celiac axis angiography, immunologic tests for tumor-associated antigens, peptide hormone assays, and cytologic study of duodenal juice is discussed. The place of palliative surgery in the management of cancer of the gallbladder is outlined. Means of improving the current high mortality of this condition are evaluated, and a plea is made for a controlled trial of the various forms of treatment that have been suggested.

Adult↗
PubMed1979

Proteins of the kidney microvillar membrane. Immunoelectrophoretic analysis of the membrane hydrolases: identification and resolution of the detergent- and proteinase-solubilized forms.

Antibodies raised in rabbits to detergent-solubilized pig kidney microvillar proteins have been used to investigate the membrane hydrolases by crossed immunoelectrophoresis. Eight enzymes were detected by specific staining methods: aminopeptidase M, dipeptidylpeptidase IV, neutral endopeptidase, aminopeptidase A, carboxypeptidase P, gamma-glutamyltransferase, trehalase and phosphodiesterase I. The mobility of all these enzymes, with the exception of trehalase and neutral endopeptidase, was increased by treatment of the detergent-solubilized preparation with papain. The difference between the detergent and proteinase forms of these enzymes is attributed to the removal of a small, non-antigenic peptide to which detergent is bound in significant quantities. This interpretation was further supported by experiments in which the microvillus fraction was labelled with an intramembrane photolabelling reagent, 1-azido-4-[125I]iodobenzene. After photolysis, the radioactivity in the membrane could be solubilized by detergent treatment but not by papain treatment. Radioautography after crossed charge-shift immunoelectrophoresis showed a good correlation between charge-shift (signifying the presence of detergent bound to a hydrophobic domain) and the presence of the label.

Animals↗
PubMed2026

PSMB8: an immune-related prognostic marker for low-grade gliomas.

BACKGROUND: Glioma is the most common primary intracranial tumor in adults. As a subunit of immune proteasome, proteasome subunit beta type-8 (PSMB8) may regulate the progression of glioma via participating in degradation and presentation of tumor antigenic peptides, but its prognostic and clinical applicant usage is under investigation. Therefore, this study aimed to comprehensively evaluate the prognostic significance of PSMB8 in low-grade glioma (LGG) and to elucidate its association with the tumor immune microenvironment and potential as a predictor for immunotherapy response. METHODS: Transcriptome data were downloaded from The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), Gene Expression Omnibus (GEO) repositories. The correlations between PSMB8 expression and the clinicopathological features of LGG were investigated in our study, and the prognostic role of PSMB8 in LGGs was assessed fully and comprehensively. Furthermore, we evaluated the correlation between PSMB8 expression and LGG immune environment via the experiments and bioinformatic analysis. RESULTS: Our results indicated that, PSMB8 were highly expressed in most tumor tissues, including LGG. Lower expression of PSMB8 was significantly correlated with lower World Health Organization (WHO) grade and isocitrate dehydrogenase (IDH) mutation status. Moreover, PSMB8 showed a promising prognostic ability for LGG patients via nomogram model and receiver operating characteristic (ROC) curves. Association analysis showed that PSMB8 expression was associated with immune cell infiltration in a variety of tumors, including LGG. Our experiments validated the positive correlation between PSMB8 expression and M2-macrophage infiltration level in clinical LGG tissues and invasive ability of LGG cell. CONCLUSIONS: PSMB8 could be used as one of the prognostic indicators of LGG and it could regulate the LGG cell migratory and invasive ability. Besides, PSMB8 is expected to be a promising biomarker of cancer immunotherapy.

Low-grade glioma (LGG)↗
PubMed1978

Three species of polyoma virus tumor antigens share common peptides probably near the amino termini of the proteins.

Detergent extracts of polyoma virus-infected mouse cells contain three major proteins of approximately 100,000--108,000 (100K), 55,000 (55K) and 21,500 (22K) daltons, which react with sera obtained from rats carrying tumors induced by the virus. A comparison of the 35S-methionine-, 3H-leucine- and 3H-proline-labeled tryptic peptides of each of these proteins by cation-exchange chromatography followed by descending paper chromatography has shown that: at least five peptides are shared by all three T-reactive proteins; at least three peptides are shared by the 55K and 22K proteins, but not by the 100K protein; at least three peptides are found only in the 22K protein; at least six peptides are found only in the 55K protein; and at least sixteen peptides are found only in the 100K protein. The results are consistent with the hypothesis that the polypeptide chains of the 100K, 55K and 22K dalton tumor antigens of polyoma virus share a common virus-coded amino terminal region. The data also suggest that there is a portion of the polypeptide chains (probably immediately adjacent to the common amino terminal region of the molecules) that is shared by the 55K and 22K proteins, but not by the 100K protein (perhaps because this portion of the genetic information is spliced out of the messenger RNA coding for the 100K protein). The facts that all the peptides common to the 100K and 55K proteins are also found in the 22K protein and are thus assigned to the common amino terminal region of the molecules, and that there are several peptides unique to the 100K protein, as well as several peptides unique to the 55K protein, suggest that the presumed carboxy terminal portion of the polypeptide chain of the 100K protein is considerably, if not entirely, different from that of the 55K protein.

Amino Acid Sequence↗