CTL recognition of a bulged viral peptide involves biased TCR selection

MHC class I molecules generally present peptides of 8-10 aa long, forming an extended coil in the HLA cleft. Although longer peptides can also bind to class I molecules, they tend to bulge from the cleft and it is not known whether the TCR repertoire has sufficient plasticity to recognize these determinants during the antiviral CTL response. In this study, we show that unrelated individuals infected with EBV generate a significant CTL response directed toward an HLA-B*3501-restricted, 11-mer epitope from the BZLF1 Ag. The 11-mer determinant adopts a highly bulged conformation with seven of the peptide side chains being solvent-exposed and available for TCR interaction. Such a complex potentially creates a structural challenge for TCR corecognition of both HLA-B*3501 and the peptide Ag. Surprisingly, unrelated B*3501 donors recognizing the 11-mer use identical or closely related alpha beta TCR sequences that share particular CDR3 motifs. Within the small number of dominant CTL clonotypes observed, each has discrete fine specificity for the exposed-side chain residues of the peptide. The data show that bulged viral peptides are indeed immunogenic but suggest that the highly constrained TCR repertoire reflects a limit to TCR diversity when responding to some unusual MHC peptide ligands.

Effect of soil type on burrowing behavior and cocoon formation in the green-striped burrowing frog, Cyclorana alboguttata

This study examined the effect of soil type on burrowing behaviour and cocoon formation during aestivation in the green-striped burrowing frog, Cyclorana alboguttata (Gunther, 1867). Given a choice, frogs always chose to burrow in wet sand in preference to wet clay. Frogs buried themselves faster and dug deeper burrows in sandy soil. However, under my laboratory conditions, there was little difference in the pattern of soil drying between the two soil types. Frogs in both sand and clay soil experienced hydrating conditions for the first 3amonths and dehydrating conditions for the last 3amonths of the 6-month aestivation period, and cocoons were not formed until after 3amonths of aestivation. After 6amonths, there were more layers in the cocoons of frogs aestivating in sand than those aestivating in clay. Frogs were able to absorb water from sandy soil with water potentials greater than -400akPa, but lost water when placed on sand with a water potential of -1000akPa.

Engineered T cell receptors and their potential in molecular medicine

T cell receptors are among the most specific biological structures found in nature and are therefore excellent candidates for the molecular targeting of antigen. It is becoming increasingly apparent that common sets of T cell receptors are frequently used in humans to combat pathogen and cancer derived threats. Given that many of these conserved T cell receptors have high affinity for their target ligands, there is potential to amass virtual banks of “off-the-shelf” receptors for use in a wide range of immunotherapeutic strategies. Additionally, such T cell receptors could become basic blueprints for artificial enhancement through mutagenesis, thereby creating an even better 3-dimensional fit for their cognate targets. Indeed, preliminary approaches using both “natural” and “supernatural” T cell receptors have shown promise in treating autoimmunity and malignancy. This review will discuss these studies and other approaches through which T cell receptors can be exploited in immunodiagnostics, pathogen control and gene therapy.

Respiration by buried echidnas Tachyglossus aculeatus

Short-beaked echidnas have an impressive ability to submerge completely into soil or sand and remain there, cryptic, for long periods. This poses questions about how they manage their respiration, cut off from a free flow of gases. We measured the gradient in oxygen partial pressure (P-O2) away from the snouts of buried echidnas and oxygen consumption (V-O2) in five individuals under similar conditions, in two substrates with different air-filled porosities (f(a)). A theoretical diffusion model indicated that diffusion alone was insufficient to account for the flux of oxygen required to meet measured rates of V-O2. However, it was noticed that echidnas often showed periodic movements of the anterior part of the body, as if such movements were a deliberate effort to flush the tidal air space surrounding their nostrils. These 'flushing movements' were subsequently found to temporarily increase the levels of interstitial oxygen in the soil around the head region. Flushing movements were more frequent while V-O2 was higher during the burrowing process, and also in substrate with lower fa. We conclude that oxygen supply to buried echidnas is maintained by diffusion through the soil augmented by periodic flushing movements, which ventilate the tidal airspace that surrounds the nostrils.

Thelastomatoidea (Nematoda : Oxyurida) of the Australian giant burrowing cockroach, Macropanesthia rhinoceros (Blaberidae : Geoscapheinae)

The thelastomatoid fauna of Macropanesthia rhinoceros was examined from 13 localities across its range in Queensland, Australia. Nine species of thelastomatoids, including two representing new genera, Geoscaphenema megaovum n. g., n. sp. and Jaidenema rhinoceratum n. g., n. sp., were found. Macropanesthia rhinoceros is reported as a new host for seven species previously recorded from Panesthia cribrata (Blaberidae: Panesthiinae) and P. tryoni tryoni, viz, Blattophila sphaerolaima, Leidynemella fusiformis, Cordonicola gibsoni, Travassosinema jaidenae, Coronostoma australiae, Hammerschmidtiella hochi and Desmicola ornata. Overall estimated richness for the system ranged from 10.1-13.5 species. The high degree of parasite faunal overlap between M. rhinoceros and the two Panesthia species is surprising given the disparate ecological niches that they occupy; P. cribrata and P. tryoni tryoni burrow in, and feed upon, moist decaying wood and require a climate that is moist all year round, whereas M. rhinoceros burrows in loose soil, feeds on fallen leaf litter and is tolerant of much drier environments.

Beta-lactam allergy in adults with cystic fibrosis

Background: Allergic reactions to one or more beta-lactam antibiotic can pose a management problem in patients with cystic fibrosis (CF), and may limit antibiotic choice. Method: The aim of this study was to assess the prevalence of allergy to anti-pseudomonal beta-lactam antibiotics in an adult CF centre and to assess variables, which may contribute to the development of allergic reactions. A questionnaire-based interview and a review of medical records were performed. Results: Of the 150 patients, 54 (36%) had allergic reactions to one or more beta-lactam antibiotics and 20 (19%) had allergic reactions to multiple beta-lactam antibiotics. The proportion of patients allergic to specific beta-lactam antibiotics varied from 10% to 26%. Rates of reactions were highest for penicillins and cephalosporins, intermediate for carbepenems and lowest for aztreonam. Of all reactions, 40% occurred within 24 h of the commencement of an individual antibiotic course. Patients with one or more beta-lactam allergic reactions had received greater cumulative exposure (p < 0.0001), were older (p=0.016) and had lower lung function (p=0.037) than patients without a history of beta-lactam allergy. Cystic Fibrosis transmembrane regulator (CFTR) status, gender, peripheral blood eosinophil count and total IgE concentrations were not different in patients with allergic reactions. Conclusions: This study demonstrates that the prevalence of allergic reactions to beta-lactam antibiotics is high in adults with CF. Increasing age; cumulative exposure and decreasing FEV1 were associated with the development of allergy. (C) 2006 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Plasma Epstein-Barr virus (EBV) DNA is a biomarker for EBV-positive Hodgkin's lymphoma

Purpose: Latent Epstein-Barr virus (EBV) genomes are found in the malignant cells of approximately one-third of Hodgkin's lymphoma (HL) cases. Detection and quantitation of EBV viral DNA could potentially be used as a biomarker of disease activity. Experimental Design: Initially, EBV-DNA viral load was prospectively monitored from peripheral blood mononuclear cells (PBMC) in patients with HL. Subsequently, we analyzed viral load in plasma from a second cohort of patients. A total of 58 patients with HL (31 newly diagnosed, 6 relapsed, and 21 in long-term remission) were tested. Using real-time PCR, 43 PBMC and 52 plasma samples were analyzed. Results: EBV-DNA was detectable in the plasma of all EBV-positive patients with HL prior to therapy. However, viral DNA was undetectable following therapy in responding patients (P = 0.0156), EBV-positive HL patients in long-term remission (P = 0.0011), and in all patients with EBV-negative HL (P = 0.0238). Conversely, there was no association seen for the EBV-DNA load measured from PBMC in patients with active EBV-positive HL patients as compared with EBV-negative HL, or patients in long-term remission. EBV-DNA load in matched plasma/PBMC samples were not correlated. Conclusions: We show that free plasma EBV-DNA has excellent sensitivity and specificity, and can be used as a noninvasive biomarker for EBV-positive HL and that serial monitoring could predict response to therapy. Additional prospective studies are required to further evaluate the use of free plasma EBV-DNA as a biomarker for monitoring response to treatment in patients with EBV-positive HL.