Different T cell receptor affinity thresholds and CD8 coreceptor dependence govern cytotoxic T lymphocyte activation and tetramer binding properties

T cells have evolved a unique system of ligand recognition involving an antigen T cell receptor (TCR) and a coreceptor that integrate stimuli provided by the engagement of peptide-major histocompatibility complex (pMHC) antigens. Here, we use altered pMHC class I (pMHCI) molecules with impaired CD8 binding (CD8-null) to quantify the contribution of coreceptor extracellular binding to (i) the engagement of soluble tetrameric pMHCI molecules, (ii) the kinetics of TCR/pMHCI interactions on live cytotoxic T lymphocytes (CTLs), and (iii) the activation of CTLs by cell-surface antigenic determinants. Our data indicate that the CD8 coreceptor substantially enhances binding efficiency at suboptimal TCR/pMHCI affinities through effects on both association and dissociation rates. Interestingly, coreceptor requirements for efficient tetramer labeling of CTLs or for CTL activation by determinants displayed on the cell surface operated in different TCR/pMHCI affinity ranges. Wild-type and CD8-null pMHCI tetramers required monomeric affinities for cognate TCRs of KD < approximately 80 microM and approximately 35 microM, respectively, to label human CTLs at 37 degrees C. In contrast, activation by cellular pMHCI molecules was strictly dependent on CD8 binding only for TCR/pMHCI interactions with KD values >200 microM. Altogether, our data provide information on the binding interplay between CD8 and the TCR and support a model of CTL activation in which the extent of coreceptor dependence is inversely correlated to TCR/pMHCI affinity. In addition, the results reported here define the range of TCR/pMHCI affinities required for the detection of antigen-specific CTLs by flow cytometry.     

Adventitious feather replacement favours a more rapid regeneration of primaries over rectrices in two passerine bird species

There is increasing evidence of adaptive preferential investment during moult in those feather tracts that are more advantageous for fitness. In this study, we assessed whether, after the manual removal of two functionally different flight feathers (one primary and one rectrix), birds from two common passerine species (Eurasian Blackcap Sylvia atricapilla and European Robin Erithacus rubecula) favoured the regeneration of primary (supposedly the most functionally important feathers) over rectrix feathers. Our results did not show differences between replaced primary and rectrix feathers in their final length, but demonstrated that the gap left by the loss of the primary feather was filled earlier, suggesting that a rapid repair of the most essential feather tracts is also evolutionarily advantageous during the adventitious replacement of plumage.     

Larval life history strategies of sub-tropical southern African estuarine brachyuran crabs and implications for tidal inlet management

Soon after hatching the larvae of many estuarine crabs migrate from estuaries to adjacent coastal waters soon, where larval development is completed before the post larval stages recruit to estuaries to settle. This study investigated the larval flux of several brachyuran crabs resident within a subtropical estuary on the east coast of South Africa. Plankton sampleswere collected over two intensive sampling periods during the spring of1997 (19 days) and the summer of 1998 (26 days). Larvae were releasedmaximally when high tide within the estuary was crepuscular, whilerecruitment occurred during nocturnal flood tides, with peak abundanceson the maximum amplitude nocturnal flood tides. The data are discussedin relation to freshwater inflow problems facing South African estuaries andthe active management of the tidal inlets of affected systems.     

Common principle of guidance by echolocation and vision

1. Using echolocation, bats move as gracefully as birds through the cluttered environment, suggesting common principles of optic and acoustic guidance. We tested the idea by analysing braking control of bats (Macroderma gigas) flying through a narrow aperture with eyes covered and uncovered. 2. Though braking control would seem to require rapid detection of distance and velocity and computation of deceleration, simpler control is possible using the tau function of any sensory variable S that is a power function of distance to aperture. Tau function of S is tau (S) = S/S (the dot means time derivative). Controlled braking is achievable by keeping tau (S) constant. 3. Previous experiments indicated the tau (S) constant procedure is followed by humans and birds in visually controlling braking. Analysis of the bats' flight trajectories indicated they too followed the braking procedure using echolocation. 4. The tau function of echo-delay or of echo-intensity or of angle subtended by directions of echoes from two points on the approach surface could be used to control braking. Aperture size was modulated during flight on some trials in an attempt to test between these possibilities, but the results were inconclusive.     

Full Text and Figure Display Improves Bioscience Literature Search

When reading bioscience journal articles, many researchers focus attention on the figures and their captions. This observation led to the development of the BioText literature search engine [1], a freely available Web-based application that allows biologists to search over the contents of Open Access Journals, and see figures from the articles displayed directly in the search results. This article presents a qualitative assessment of this system in the form of a usability study with 20 biologist participants using and commenting on the system. 19 out of 20 participants expressed a desire to use a bioscience literature search engine that displays articles'' figures alongside the full text search results. 15 out of 20 participants said they would use a caption search and figure display interface either frequently or sometimes, while 4 said rarely and 1 said undecided. 10 out of 20 participants said they would use a tool for searching the text of tables and their captions either frequently or sometimes, while 7 said they would use it rarely if at all, 2 said they would never use it, and 1 was undecided. This study found evidence, supporting results of an earlier study, that bioscience literature search systems such as PubMed should show figures from articles alongside search results. It also found evidence that full text and captions should be searched along with the article title, metadata, and abstract. Finally, for a subset of users and information needs, allowing for explicit search within captions for figures and tables is a useful function, but it is not entirely clear how to cleanly integrate this within a more general literature search interface. Such a facility supports Open Access publishing efforts, as it requires access to full text of documents and the lifting of restrictions in order to show figures in the search interface.     

Genetic and structural basis for selection of a ubiquitous T cell receptor deployed in Epstein-Barr virus infection

Despite the ～10(18) αβ T cell receptor (TCR) structures that can be randomly manufactured by the human thymus, some surface more frequently than others. The pinnacles of this distortion are public TCRs, which exhibit amino acid-identical structures across different individuals. Public TCRs are thought to result from both recombinatorial bias and antigen-driven selection, but the mechanisms that underlie inter-individual TCR sharing are still largely theoretical. To examine this phenomenon at the atomic level, we solved the co-complex structure of one of the most widespread and numerically frequent public TCRs in the human population. The archetypal AS01 public TCR recognizes an immunodominant BMLF1 peptide, derived from the ubiquitous Epstein-Barr virus, bound to HLA-A*0201. The AS01 TCR was observed to dock in a diagonal fashion, grasping the solvent exposed peptide crest with two sets of complementarity-determining region (CDR) loops, and was fastened to the peptide and HLA-A*0201 platform with residue sets found only within TCR genes biased in the public response. Computer simulations of a random V(D)J recombination process demonstrated that both TCRα and TCRβ amino acid sequences could be manufactured easily, thereby explaining the prevalence of this receptor across different individuals. Interestingly, the AS01 TCR was encoded largely by germline DNA, indicating that the TCR loci already comprise gene segments that specifically recognize this ancient pathogen. Such pattern recognition receptor-like traits within the αβ TCR system further blur the boundaries between the adaptive and innate immune systems.