Human and murine clonal CD8+ T cell expansions arise during tuberculosis because of TCR selection

The immune system can recognize virtually any antigen, yet T cell responses against several pathogens, including Mycobacterium tuberculosis, are restricted to a limited number of immunodominant epitopes. The host factors that affect immunodominance are incompletely understood. Whether immunodominant epitopes elicit protective CD8+ T cell responses or instead act as decoys to subvert immunity and allow pathogens to establish chronic infection is unknown. Here we show that anatomically distinct human granulomas contain clonally expanded CD8+ T cells with overlapping T cell receptor (TCR) repertoires. Similarly, the murine CD8+ T cell response against M. tuberculosis is dominated by TB10.44-11-specific T cells with extreme TCRß bias. Using a retro genic model of TB10.44-11-specific CD8+ Tcells, we show that TCR dominance can arise because of competition between clonotypes driven by differences in affinity. Finally, we demonstrate that TB10.4-specific CD8+ T cells mediate protection against tuberculosis, which requires interferon-? production and TAP1-dependent antigen presentation in vivo. Our study of how immunodominance, biased TCR repertoires, and protection are inter-related, provides a new way to measure the quality of T cell immunity, which if applied to vaccine evaluation, could enhance our understanding of how to elicit protective T cell immunity.

The family haloplasmataceae

Haloplasmataceae is a family within the order Haloplasmatales, which currently includes one single genus and species: Haloplasma contractile. This family has unusual phenotypic features the most noticeable being a unique morphology and cellular contractility cycle and a distinct phylogenetic position between the Firmicutes and the Tenericutes (Mollicutes). Members of the Haloplasmataceae have been isolated from the upper sediments of a deep-sea anoxic brine in the Red Sea, but cultivation-independent studies have found related sequences in a wide range of biotopes including other extreme environments, contaminated soils and marine sediments, as well as intestinal samples. The isolation and description of new representatives of this family might therefore result in significant changes to the current description.

The Family Salinisphaeraceae

The family Salinisphaeraceae (Class Gammaproteobacteria, Order Salinisphaerales) comprises a single genus, Salinisphaera, and six species: S. shabanensis, S. hydrothermalis, S. dokdonensis, S. orenii, S. halophila, and S. japonica. All members of the family Salinisphaeraceae were isolated from marine/oceanic and high-salinity environments. These bacteria have coccoid or short rod morphologies and are halophilic or halotolerant. All known members of the family Salinisphaeraceae are heterotrophic, mesophilic aerobes, although S. hydrothermalis was shown to be a facultative chemolithoautotroph. Isolation and characterization of new members of the Salinisphaeraceae, as well as in-depth studies of the currently known species, will allow for a better understanding of this family.

Quantifying the legacy of the Chinese Neolithic on the maternal genetic heritage of Taiwan and Island Southeast Asia

There has been a long-standing debate concerning the extent to which the spread of Neolithic ceramics and Malay-Polynesian languages in Island Southeast Asia (ISEA) were coupled to an agriculturally driven demic dispersal out of Taiwan 4000 years ago (4 ka). We previously addressed this question using founder analysis of mitochondrial DNA (mtDNA) control-region sequences to identify major lineage clusters most likely to have dispersed from Taiwan into ISEA, proposing that the dispersal had a relatively minor impact on the extant genetic structure of ISEA, and that the role of agriculture in the expansion of the Austronesian languages was therefore likely to have been correspondingly minor. Here we test these conclusions by sequencing whole mtDNAs from across Taiwan and ISEA, using their higher chronological precision to resolve the overall proportion that participated in the "out-of-Taiwan" mid-Holocene dispersal as opposed to earlier, postglacial expansions in the Early Holocene. We show that, in total, about 20 % of mtDNA lineages in the modern ISEA pool result from the "out-of-Taiwan" dispersal, with most of the remainder signifying earlier processes, mainly due to sea-level rises after the Last Glacial Maximum. Notably, we show that every one of these founder clusters previously entered Taiwan from China, 6-7 ka, where rice-farming originated, and remained distinct from the indigenous Taiwanese population until after the subsequent dispersal into ISEA.