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Peptide Presentation (peptide + presentation)

Distribution by Scientific Domains

Chemistry	50%

Selected Abstracts

Crystal structure of HLA-A*2402 complexed with a telomerase peptide

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 1 2006
David
Abstract HLA-A*2402 is the most commonly expressed HLA allele in oriental populations. It is also widely expressed in the Caucasian population, making it one of, if not the most abundant HLA,I types. In order to study its structure in terms of overall fold and peptide presentation, a soluble form of this HLA,I (,1, ,2, ,3 and ,2m domains) has been expressed, refolded and crystallized in complex with a cancer-related telomerase peptide (VYGFVRACL), and its structure has been solved to 2.8,Å resolution. The overall structure of HLA-A*2402 is virtually identical to other reported peptide-HLA,I structures. However, there are distinct features observable from this structure at the HLA,I peptide binding pockets. The size and depth of pocket,B makes it highly suitable for binding to large aromatic side chains, which explains the high prevalence of tyrosine at peptide position,2. Also, for HLA binding at peptide position,5, there is an additional anchor point, which allows the proximal amino acids to protrude out, providing a prominent feature for TCR interaction. Finally, pocket,F allows the anchor residue at position,9 to be bound unusually deeply within the HLA structure. [source]

Dissecting cytotoxic T,cell responses towards the NY-ESO-1 protein by peptide/MHC-specific antibody fragments

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 10 2004
Gerhard Held
Abstract NY-ESO-1 is a germ cell antigen aberrantly expressed by different tumor types that elicits strong humoral and cellular immune responses, representing one of the most promising candidates for vaccination of cancer patients. A detailed analysis of CD8+ T,cells generated in vaccine trials using NY-ESO-1-derived peptides (157,165 and 157,167) revealed that the dominant immune response was directed against a cryptic epitope (159,167) diverting the immune response from tumor recognition. Only CTL reactivity to the NY-ESO-1157,165 peptide appeared to be capable of lysing NY-ESO-1/HLA-A0201-expressing tumor cells. To study the process of NY-ESO-1 peptide presentation by tumor cells in more detail we generated a high-affinity (KD=60,nM) antibody fragment that specifically recognizes the NY-ESO-1157,165 peptide/HLA-A0201 complex. Peptide variants such as the NY-ESO-1157,167 peptide or the cryptic NY-ESO-1159,167 peptide were not recognized. The antibody fragment blocked in a dose-dependent fashion the recognition of NY-ESO-1/HLA-A2-positive tumor cells by NY-ESO-1157,165 peptide-specific CD8+ T,cells. This antibody fragment is a novel reagent that binds with TCR-like specificity to the NY-ESO-1157,165/HLA-A2 complex thus distinguishing between CTL responses against immunological meaningful or cryptic NY-ESO-1-derived peptides. It may therefore become a useful monitoring tool for the development of NY-ESO-1-based cancer vaccines. [source]

Altering the surface properties of baculovirus Autographa californica NPV by insertional mutagenesis of the envelope protein gp64

FEBS JOURNAL, Issue 18 2002
Alexandra Spenger
The envelope protein gp64 of the baculovirus Autographa californica nuclear polyhedrosis virus is essential for viral entry into insect cells, as the glycoprotein both mediates pH-dependent membrane fusion and binds to host cell receptors. Surface modification of baculovirus particles by genetic engineering of gp64 has been demonstrated by various strategies and thus has become an important and powerful tool in molecular biology. To improve further the presentation of peptides on the surface of baculovirus particles, several insertion sites within the gp64 envelope protein were selected by their theoretical maximum surface probability and investigated for efficient peptide presentation. The ELDKWA peptide of the gp41 of HIV-1, specific for the human mAb 2F5, was inserted into 17 different positions of the glycoprotein gp64. Propagation of viruses was successful in 13 cases, mutagenesis at four positions did not result in production of intact virus particles. Western blotting, FACS analysis and ELISA were used for characterization of the different binding properties of the mutants. Insertion of this peptide into the native envelope protein resulted in high avidity display on the surface of baculovirus particles. This approach offers the possibility of effective modification of surface properties in regard to host range specificity and antigen display. [source]

Binding interactions between peptides and proteins of the class II Major Histocompatibility Complex

MEDICINAL RESEARCH REVIEWS, Issue 2 2002
Benjamin J. McFarland
Abstract The activation of helper T cells by peptides bound to proteins of the class II Major Histocompatibility Complex (MHC II) is pivotal to the initiation of an immune response. The primary functional requirement imposed on MHC II proteins is the ability to efficiently bind thousands of different peptides. Structurally, this is reflected in a unique architecture of binding interactions. The peptide is bound in an extended conformation within a groove on the membrane distal surface of the protein that is lined with several pockets that can accommodate peptide side-chains. Conserved MHC II protein residues also form hydrogen bonds along the length of the peptide main-chain. Here we review recent advances in the study of peptide-MHC II protein reactions that have led to an enhanced understanding of binding energetics. These results demonstrate that peptide-MHC II protein complexes achieve high affinity binding from the array of hydrogen bonds that are energetically segregated from the pocket interactions, which can then add to an intrinsic hydrogen bond-mediated affinity. Thus, MHC II proteins are unlike antibodies, which utilize cooperativity among binding interactions to achieve high affinity and specificity. The significance of these observations is discussed within the context of possible mechanisms for the HLA-DM protein that regulates peptide presentation in vivo and the design of non-peptide molecules that can bind MHC II proteins and act as vaccines or immune modulators. © 2002 John Wiley & Sons, Inc. Med Res Rev, 22, No. 2, 168,203, 2002; DOI 10.1002/med.10006 [source]