Amino Acid Similarity Accounts for T Cell Cross-Reactivity and for “Holes” in the T Cell Repertoire

Background: Cytotoxic T cell (CTL) cross-reactivity is believed to play a pivotal role in generating immune responses but the extent and mechanisms of CTL cross-reactivity remain largely unknown. Several studies suggest that CTL clones can recognize highly diverse peptides, some sharing no obvious sequence identity. The emerging realization in the field is that T cell receptors (TcR) recognize multiple distinct ligands. Principal Findings: First, we analyzed peptide scans of the HIV epitope SLFNTVATL (SFL9) and found that TCR specificity is position dependent and that biochemically similar amino acid substitutions do not drastically affect recognition. Inspired by this, we developed a general model of TCR peptide recognition using amino acid similarity matrices and found that such a model was able to predict the cross-reactivity of a diverse set of CTL epitopes. With this model, we were able to demonstrate that seemingly distinct T cell epitopes, i.e., ones with low sequence identity, are in fact more biochemically similar than expected. Additionally, an analysis of HIV immunogenicity data with our model showed that CTLs have the tendency to respond mostly to peptides that do not resemble self-antigens. Conclusions: T cell cross-reactivity can thus, to an extent greater than earlier appreciated, be explained by amino acid similarity. The results presented in this paper will help resolving some of the long-lasting discussions in the field of T cel

Situating Emotions: From Embodied Cognition to Mindreading

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Forest Decline after a 15-Year “Perfect Storm” of Invasion by Hemlock Woolly Adelgid, Drought, and Hurricanes

Invasions by introduced pests can interact with other disturbances to alter forests and their functions, particularly when a dominant tree species declines. To identify changes after invasion by the insect hemlock woolly adelgid (Adelges tsugae; HWA), coinciding with severe droughts and hurricanes, this study compared tree species composition of eastern hemlock (Tsuga canadensis) forests on 11 plots before (2001) and 15 years after (2016) invasion in the southern Appalachian Mountains, USA. Losses of hemlock trees after HWA invasion were among the highest reported, with a 90% decline in density, 86% decline in basal area, and 100% mortality for individuals ≥ 60 cm in diameter. In contrast to predictions of theoretical models, deciduous tree density declined after HWA invasion, while basal area changed little, at least during the initial 15 years after invasion. Overall, forest density declined by 58%, basal area by 25%, and tree species richness by 8%. Factors additional to HWA likely exacerbating forest decline included: droughts before (1999–2001) and after HWA invasion (2006–2008); tree uprooting from hurricane-stimulated winds in 2004; pest-related declines of deciduous tree species otherwise likely benefitting from hemlock’s demise; death of deciduous trees when large hemlocks fell; and competition from aggressive understory plants including doghobble (Leucothoe fontanesiana), rosebay rhododendron (Rhododendron maximum), and Rubus spp. Models of forest change and ecosystem function should not assume that deciduous trees always increase during the first decades after HWA invasion