Volume 13 Issue 6, June 2012

Protection against recurrent infections requires the generation of memory B cells and persistent antibody production. An adaptor complex of DOCK8-MyD88-Pyk2 now links signaling via TLR9 to activation of the transcription factor STAT3 and the establishment of serological memory.

Immunosurveillance monitors subversion of the endoplasmic reticulum aminopeptidase ERAAP. ERAAP-deficient cells are killed by T cells that recognize nonclassical major histocompatibility complex class I Qa-1 molecules presenting peptides generated in the absence of ERAAP.

The role of the coreceptor CD28 in thymic clonal deletion has been controversial. New evidence suggests that CD28 deficiency impairs the clonal deletion of self-reactive T cells but also results in their developmental diversion to an anergic lineage that ends up in the gut.

A previously unknown protein, Tespa1, that regulates the thymocyte positive-selection checkpoint has now been identified. The phenotype of Tespa1-deficient mice and the role of Tespa1 in thymocyte signaling are very similar to those of Themis-deficient mice and Themis itself, another recently described but unrelated protein.

The eukaryotic translation-initiation factor eIF4E is a rate-limiting factor in protein translation. Sonenberg and colleagues show that phosphorylation of eIF4E modulates the antiviral response by selectively stimulating translation of the NF-κB inhibitor IκBα

Major histocompatibility complex (MHC) molecules are known to mediate reverse signaling. Cao and colleagues show that reverse signaling via MHC class I attenuates Toll-like receptor–triggered innate inflammatory responses through an Fps–SHP-2 pathway.

Positive selection of thymocytes is controlled by TCR expression and signaling. Lu and colleagues describe a previously uncharacterized protein, Tespa1, which associates with TCR signaling components and has a critical role in positive selection.

The role of costimulation in negative selection is controversial. Singer and colleagues demonstrate that it is critical for clonal deletion and its absence results in the diversion of thymocytes to an intraepithelial lymphocyte population.

The aminopeptidase ERAAP trims peptides loaded onto MHC class I molecules and can be targeted during evasion of the immune response by pathogens. Shastri and colleagues show that inhibition of ERAAP identifies a protective nonclassical MHC presentation pathway involving Qa-1.

Polarized CD4⁺ T cells can demonstrate considerable plasticity depending on the cytokine milieu they encounter. O'Shea and colleagues show that retinoic acid induces the microRNA miR-10a, which suppresses the transcription factor Bcl-6 to prevent conversion into follicular helper T cells.

TRIM28 is a nuclear protein associated with repressive heterochromatin. Honjo and colleagues show that loss of TRIM28 in T cells alters peripheral T cell homeostasis and regulatory T cell function, which leads to autoimmunity.

Activated B cells can tailor their ensuing antibody responses by isotype switching. McHeyzer-Williams and colleagues demonstrate B cell–intrinsic requirements for the transcription factors T-bet and RORα in maintaining IgG2a⁺ and IgA⁺ memory cells, respectively.

Dock8 deficiency leads to defects in humoral immunity. Geha and colleagues show that Dock88 interacts with MyD88 to bridge TLR9 signaling to the Src-Syk-STAT3 pathway to promote B cell proliferation and differentiation.