Opinion in 2012

There has been a tendency to associate the development of distinct CD4⁺T cell subsets with the expression of 'master regulator' transcription factors. Here, the authors discuss the shortcomings of this model and explain why 'lineage-specifying' may be a more fitting way to describe these key transcription factors.

In this Opinion, the authors describe an unconventional form of peptide recognition that can allow potentially autoreactive CD4⁺T cells to escape thymic regulation. They explain how these T cells respond to unstable peptide—MHC complexes that evade H2-DM-mediated editing, and they discuss the implications for autoimmunity.

T cells must recognize a vast array of potential foreign peptide–MHC complexes. Comprehensive immune cover can only be provided if each T cell recognizes numerous peptides. The implications of this T cell cross-reactivity include autoimmune disease but also provide opportunities for multiple therapeutic interventions.

The development of effective antiretroviral therapies has greatly improved the disease prognosis for patients with HIV. However, the limitations of these therapies have renewed interest in developing alternative treatment strategies. Here, a group of experts from the International AIDS Society discuss the research steps that need to be taken to achieve the ultimate objective — a cure for HIV.

In this Opinion article, Blander and Sander examine how the immune system is able to distinguish between viable and dead, pathogenic and non-pathogenic, or invading and colonizing microorganisms. They propose five immune checkpoints that can be used to determine the relative threat of a particular microbial encounter.