Immediate Early and Early Lytic Cycle Proteins Are Frequent Targets of the Epstein-Barr Virus–induced Cytotoxic T Cell Response

Epstein-Barr virus (EBV), a human γ-herpesvirus, can establish both nonproductive (latent) and productive (lytic) infections. Although the CD8+ cytotoxic T lymphocyte (CTL) response to latently infected cells is well characterized, very little is known about T cell controls over lytic infection; this imbalance in our understanding belies the importance of virus-replicative lesions in several aspects of EBV disease pathogenesis. The present work shows that the primary CD8+ CTL response to EBV in infectious mononucleosis patients contains multiple lytic antigen-specific reactivities at levels at least as high as those seen against latent antigens; similar reactivities are also detectable in CTL memory. Clonal analysis revealed individual responses to the two immediate early proteins BZLF1 and BRLF1, and to three (BMLF1, BMRF1, and BALF2) of the six early proteins tested. In several cases, the peptide epitope and HLA-restricting determinant recognized by these CTLs has been defined, one unusual feature being the number of responses restricted through HLA-C alleles. The work strongly suggests that EBVreplicative lesions are subject to direct CTL control in vivo and that immediate early and early proteins are frequently the immunodominant targets. This contrasts with findings in α- and β-herpesvirus systems (herpes simplex, cytomegalovirus) where viral interference with the antigen-processing pathway during lytic infection renders immediate early and early proteins much less immunogenic. The unique capacity of γ-herpesvirus to amplify the viral load in vivo through a latent growth-transforming infection may have rendered these agents less dependent upon viral replication as a means of successfully colonizing their hosts

Study of doubly strange systems using stored antiprotons

Bound nuclear systems with two units of strangeness are still poorly known despite their importance for many strong interaction phenomena. Stored antiprotons beams in the GeV range represent an unparalleled factory for various hyperon-antihyperon pairs. Their outstanding large production probability in antiproton collisions will open the floodgates for a series of new studies of systems which contain two or even more units of strangeness at the P‾ANDA experiment at FAIR. For the first time, high resolution γ-spectroscopy of doubly strange ΛΛ-hypernuclei will be performed, thus complementing measurements of ground state decays of ΛΛ-hypernuclei at J-PARC or possible decays of particle unstable hypernuclei in heavy ion reactions. High resolution spectroscopy of multistrange Ξ−-atoms will be feasible and even the production of Ω−-atoms will be within reach. The latter might open the door to the |S|=3 world in strangeness nuclear physics, by the study of the hadronic Ω−-nucleus interaction. For the first time it will be possible to study the behavior of Ξ‾+ in nuclear systems under well controlled conditions

Multiple HLA A11-restricted cytotoxic T-lymphocyte epitopes of different immunogenicities in the Epstein-Barr virus-encoded nuclear antigen 4

Epstein-Barr virus (EBV), a ubiquitous herpesvirus, induces potent HLA class I-restricted cytotoxic T-lymphocyte (CTL) responses. Analyses of target antigen choice have shown that the very strong CTL responses which are often observed through the HLA A11 allele map are due almost entirely to a single transformation-associated EBV protein, the nuclear antigen EBNA4. Here, we sought to determine the number and relative immunogenicities of HLA A11-restricted epitopes within this 938-amino-acid protein. An initial screening with a series of recombinant vaccinia virus vectors encoding progressively truncated forms of EBNA4 was followed by peptide sensitization experiments using overlapping 14- or 15-mers from the entire sequence. These two approaches allowed the identification of five epitope regions located between residues 101 and 115, 416 and 429, 396 and 410, 481 and 495, and 551 and 564 of the EBNA4 molecule. CTL preparations from all seven HLA A11-positive donors tested had demonstrable reactivities against the 416-to-429 peptide, whereas reactivities against the other epitopes either tended to be lost on serial passage or, for some of the donors, were never detected. The immunodominance of the 416-to-429 epitope was further supported by peptide dilution assays using polyclonal effectors and by CTL cloning experiments. Analysis of the 416-to-429 region identified the nanomer 416-424 (IVTDFSVIK) as the cognate peptide. This peptide was able to sensitize targets to lysis by A11-restricted CTL clones at concentrations as low as 5 x 10(-14) M

Experimental access to Transition Distribution Amplitudes with the P̄ANDA experiment at FAIR

Baryon-to-meson Transition Distribution Amplitudes (TDAs) encoding valuable new information on hadron structure appear as building blocks in the collinear factorized description for several types of hard exclusive reactions. In this paper, we address the possibility of accessing nucleon-to-pion (\u3c0N) TDAs from \uafpp \u2192 e+e 12\u3c00 reaction with the future PANDA detector at the FAIR facility. At high center- of-mass energy and high invariant mass squared of the lepton pair q2, the amplitude of the signal channel pp\uaf \u2192 e+e 12\u3c00 admits a QCD factorized description in terms of \u3c0N TDAs and nucleon Distribution Amplitudes (DAs) in the forward and backward kinematic regimes. Assuming the validity of this factorized description, we perform feasibility studies for measuring \uafpp \u2192 e+e 12\u3c00 with the PANDA detector. Detailed simulations on signal reconstruction efficiency as well as on rejection of the most severe background channel, i.e. pp\uaf \u2192 \u3c0+\u3c0 12\u3c00 were performed for the center-of-mass energy squared s = 5 GeV2 and s = 10 GeV2, in the kinematic regions 3.0 0.5 in the proton-antiproton center-of-mass frame. Results of the simulation show that the particle identification capabilities of the PANDA detector will allow to achieve a background rejection factor of 5 \ub7 107 (1 \ub7 107) at low (high) q2 for s = 5 GeV2, and of 1 \ub7 108 (6 \ub7 106) at low (high) q2 for s = 10 GeV2, while keeping the signal reconstruction efficiency at around 40%. At both energies, a clean lepton signal can be reconstructed with the expected statistics corresponding to 2 fb 121 of integrated luminosity. The cross sections obtained from the simulations are used to show that a test of QCD collinear factorization can be done at the lowest order by measuring scaling laws and angular distributions. The future measurement of the signal channel cross section with PANDA will provide a new test of the perturbative QCD description of a novel class of hard exclusive reactions and will open the possibility of experimentally accessing \u3c0N TDAs

Technical Design Report for the Panda Forward Spectrometer Calorimeter

This document is devoted to the electromagnetic calorimeter of the Forward Spectrometer and describes the design considerations, the technical layout, the expected performance, and the production readiness

Technical Design Report for the Panda Forward Spectrometer Calorimeter

This document is devoted to the electromagnetic calorimeter of the Forward Spectrometer and describes the design considerations, the technical layout, the expected performance, and the production readiness

Eperimental access to Transition Distribution Amplitudes with the PANDA experiment at FAIR

We address the possibility of accessing nucleon-to-pion (πN) Transition Distribution Amplitudes (TDAs) from p¯p→e+e−π0 reaction with the future \={P}ANDA detector at the FAIR facility. At high center of mass energy and high invariant mass of the lepton pair q2, the amplitude of the signal channel p¯p→e+e−π0 admits a QCD factorized description in terms of πN TDAs and nucleon Distribution Amplitudes (DAs) in the forward and backward kinematic regimes. Assuming the validity of this factorized description, we perform feasibility studies for measuring p¯p→e+e−π0 with the \={P}ANDA detector. Detailed simulations on signal reconstruction efficiency as well as on rejection of the most severe background channel, {\it i.e.} p¯p→π+π−π0 were performed for the center of mass energy squared s=5 GeV2 and s=10 GeV2, in the kinematic regions 3.00.5 in the proton-antiproton center of mass frame. Results of the simulation show that the particle identification capabilities of the \={P}ANDA detector will allow to achieve a background rejection factor at the level of 108 (2⋅107) at low (high) q2 while keeping the signal reconstruction efficiency at around 40% and that a clean lepton signal can be reconstructed with the expected statistics corresponding to 2 fb−1 of integrated luminosity. The future measurement of the signal channel cross section with \={P}ANDA will provide a new test of perturbative QCD description of a novel class of hard exclusive reactions and will open the possibility of experimentally accessing πN TDAs