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Viral Peptide (viral + peptide)
Selected AbstractsWeak agonist self-peptides promote selection and tuning of virus-specific T cellsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 3 2003Samuel Abstract Recent progress has begun to define the interactions and signaling pathways that are triggered during positive selection. To identify and further examine self-peptides that can mediate positive selection, we searched a protein-database to find peptides that have minimal homology with the viral peptide (p33) that activates a defined P14 transgenic TCR. We identified four peptides that could bind the restriction element H-2Db and induce proliferation of P14 transgenic splenocytes at high concentration. Two of the four peptides (DBM and RPP) were able to positively select thevirus-specific TCR in fetal thymic organ culture but were unable to induce clonal deletion. Reverse-phase HPLC and mass spectrometry demonstrated that these peptides were presented by H-2Db molecules on thymic epithelial cell lines. We also examined whether the selecting ligands altered T cell responsiveness in vitro. DBM-selected T cells lost their ability to respond to the positively selecting ligand DBM, whereas RPP-selected T cells only retainrd their ability to respond to high concentrations of RPP. These results demonstrate that self-peptides that mediate positiveselection can differentially "tune" the activation threshold of T cells and alter the functional repertoire of T cells. [source] Genetic variability of hepatitis C virus NS3 protein in human leukocyte antigen-A2 liver transplant recipients with recurrent hepatitis CLIVER TRANSPLANTATION, Issue 2 2004F. Xavier López-Labrador The association between the severity of chronic hepatitis C and the variability of the hepatitis C virus (HCV) genome remains controversial, but to our knowledge few data are available to date regarding T-cell epitope coding regions in transplant patients. In the current study, we identified 21 human leukocyte antigen (HLA)-A2-positive Spanish patients with chronic hepatitis C, 14 immunosuppressed liver transplant recipients, and 7 immunocompetent controls. Alanine aminotransferase, aspartate aminotransferase, viral load, and rate of fibrosis progression were determined. Genetic distances of HCV isolates and variations in epitopes of the HCV nonstructural 3 protein (NS3-1393 LIFCHSKKK and NS3-1406 KLVALGINAV) were compared between patients with slow or fast progression of fibrosis. Isolates from transplant patients with fast progression were found to be more divergent (P =.03), had a higher mean value of synonymous (dS) variations (P =.02), and some were differentiated in a phylogenetic tree, compared with isolates from patients with slow progression. The HLA-A2-restricted NS3-1406 epitope was found to be more variable (20 of 21 isolates differed from the prototype) compared with the A3-restricted NS3-1392 epitope (19% vs. 1.25% variation). A shift in the viral peptide was not detected in a subset of transplant patients, but was evident in two of three nontransplant patients with follow-up. There was no correlation noted between a particular amino acid variation and fibrosis progression (slow or fast) in either transplant or nontransplant patients. The results of the current study suggest that 1) there may be different HCV-1b strains in our geographic area, 2) immunosuppression appears to have little effect in amino acid variation at the HCV NS3-1406 epitope, and 3) variations over time might be more frequent in nonimmunosuppressed patients. (Liver Transpl 2004;10:217,227.) [source] HLA,B27 heavy chains distinguished by a micropolymorphism exhibit differential flexibilityARTHRITIS & RHEUMATISM, Issue 4 2010Heinz Fabian Objective Although the products of the HLA subtypes B*2705 and B*2709 differ only in residue 116 (Asp versus His) within their peptide-binding grooves, they are differentially associated with inflammatory rheumatic diseases such as ankylosing spondylitis (AS): B*2705 occurs in AS patients, whereas B*2709 is only rarely encountered. The reasons for this distinct association are still unclear but could include subtype-specific conformational and dynamic properties of these antigens. The present study was undertaken to investigate structural and dynamic differences between B*2705 and B*2709 and their possible relationship to subtype-specific disease association. Methods The membrane-distal segments of the B*2705 and B*2709 heavy chains were expressed in vitro and reconstituted together with ,2 -microglobulin and a peptide. HLA,B27 complexes loaded with 2 self peptides (TIS [RRLPIFSRL] and pVIPR [RRKWRRWHL]) and a sequence-related viral peptide (pLMP2 [RRRWRRLTV]) were studied by isotope-edited infrared spectroscopy to detect differences in their structure and flexibility at physiologic temperature. Results Our analyses revealed the existence of subtype-specific conformational differences between the 2 HLA,B27 heavy chains at physiologic temperature, which are undetectable using x-ray crystallography. Irrespective of the bound peptide, the heavy chain of the B*2705 complex exhibited higher conformational flexibility than the B*2709 heavy chain. Conclusion The present study demonstrates the existence of previously undetected systematic conformational and dynamic differences between the heavy chains of the 2 HLA,B27 subtypes. Since effector cell recognition of cells expressing HLA antigens is dependent on the dynamic properties of the interacting cell surface molecules, this HLA,B27 subtype,specific heavy chain flexibility could have a role in the distinct association of HLA,B27 subtypes with spondylarthritides. [source] Expression, purification and preliminary X-ray crystallographic analysis of the human major histocompatibility antigen HLA-B*1402 in complex with a viral peptide and with a self-peptideACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 7 2007Pravin Kumar The product of the human major histocompatibility (HLA) class I allele HLA-B*1402 only differs from that of allele HLA-B*1403 at amino-acid position 156 of the heavy chain (Leu in HLA-B*1402 and Arg in HLA-B*1403). However, both subtypes are known to be differentially associated with the inflammatory rheumatic disease ankylosing spondylitis (AS) in black populations in Cameroon and Togo. HLA-B*1402 is not associated with AS, in contrast to HLA-B*1403, which is associated with this disease in the Togolese population. The products of these alleles can present peptides with Arg at position 2, a feature shared by a small group of other HLA-B antigens, including HLA-B*2705, the prototypical AS-associated subtype. Complexes of HLA-B*1402 with a viral peptide (RRRWRRLTV, termed pLMP2) and a self-peptide (IRAAPPPLF, termed pCatA) were prepared and were crystallized using polyethylene glycol as precipitant. The complexes crystallized in space groups P21 (pLMP2) and P212121 (pCatA) and diffracted synchrotron radiation to 2.55 and 1.86,Ĺ resolution, respectively. Unambiguous solutions for both data sets were obtained by molecular replacement using a peptide-complexed HLA-B*2705 molecule (PDB code 1jge) as a search model. [source] E5 protein of human papillomavirus type 16 selectively downregulates surface HLA class IINTERNATIONAL JOURNAL OF CANCER, Issue 2 2005G. Hossein Ashrafi Abstract Papillomaviruses have evolved mechanisms that result in escape from host immune surveillance. The E5 protein is expressed early in papillomavirus infection in the deep layers of the infected epithelium. It is localized to the Golgi apparatus (GA) and endoplasmic reticulum. The E5 protein of bovine papillomavirus (BPV) impairs the synthesis and stability of major histocompatibility (MHC) class I complexes and prevents their transport to the cell surface due to retention in the GA. Here we show that human papillomavirus type 16 (HPV-16) E5 also causes the retention of MHC (HLA) class I complexes in the GA and impedes their transport to the cell surface, which is rescued by treatment with interferon. Unlike BPV E5, HPV-16 E5 does not affect the synthesis of HLA class I heavy chains or the expression of the transporter associated with antigen processing TAP. These results show that downregulation of surface MHC class I molecules is common to both BPV and HPV E5 proteins. Moreover, we determined that HPV-16 E5 downregulates surface expression of HLA-A and HLA-B, which present viral peptides to MHC class I-restricted cytotoxic T lymphocytes (CTLs), but not the natural killer (NK) cell inhibitory ligands HLA-C and HLA-E. Selective downregulation of cell surface HLA class I molecules may allow the virus to establish infection by avoiding immune clearance of virus-infected cells by both CTLs and NK cells. [source] A longitudinal analysis of cytotoxic T lymphocyte precursor frequencies to the hepatitis B virus in chronically infected patientsJOURNAL OF VIRAL HEPATITIS, Issue 1 2001G. K. Sing Individuals with acute hepatitis B virus (HBV) infection characteristically mount a strong, multispecific cytotoxic T lymphocyte (CTL) response that is effective in eradicating virus. In contrast, this response in chronic carriers is usually weak or undetectable. Since it is generally acknowledged that HBV pathogenesis is immune-mediated, the occurrence of episodes of active liver disease in many carriers suggests that these individuals can mount active CTL responses to HBV. To see whether the detection of circulating CTLs is related to these flare episodes, we have determined the CTL precursor (CTLp) frequencies to HLA-A2-restricted viral peptides in seven patients over a 12,24-month period of their disease. Limiting dilution analyses (LDA) were performed longitudinally to five epitopes comprising the viral capsid (HBc), envelope (HBs) and polymerase (pol) proteins. Assays were performed against a mixture of peptides, or against each individual peptide, to measure overall CTL activity and the multispecificity of the responses, respectively. Since two of the patients were treated with recombinant human interleukin-12 (rHuIL-12) at the time, with one individual achieving complete disease remission a year later after being treated with interferon-,, we were also able to examine the effects of these cytokines on HBV cytotoxicity. Our results indicate that weak but detectable CTL responses do occur in chronic carriers which are generally associated with disease flares, although CTLps were also seen occasionally during minimal disease activity. The range of specificities varied between individuals and within each individual during the course of the disease. Finally, we also provide evidence that CTL reactivity is stimulated following treatment with certain cytokines, but is dependent on the time of administration. [source] | ||||||||||