Roles of TRAF3 in T cells: many surprises

Tumor necrosis factor receptor (TNFR)-associated factor 3 (TRAF3) is broadly involved in different receptor-mediated signaling pathways. Considerable progress was made recently in understanding the role of TRAF3 in T cell biology. Here we review these new findings about how TRAF3 participates in T cell development and function. The different roles of TRAF3 in distinct immune cells are also compared. That TRAF3 is required for T cell effector functions, and invariant Natural Killer T cell function and development, was unexpected. Another surprising finding is that TRAF3 normally restrains regulatory T cell development. It is now clear that TRAF3 regulates signaling to T cells not only through costimulatory members of the TNFR superfamily, but also through the T cell receptor complex, and cytokine receptors. The diverse roles it plays support the multifaceted nature of this molecule. How TRAF3 mediates integration of different signaling cascades is an important topic for future study.     

Technical Considerations in the Preparation of Fluorescent-Antibody Conjugates

A comparison was made of (NH₄)₂SO₄, HCl, ethodin, and ethanol for fractionation of rabbit antiserum prior to conjugation with fluorescein isothiocyanate. Fractionation with the salt was found to be the method of choice from the standpoints of simplicity and recovery of antibody effective in conjugates prepared from the fractions. Effects of pH, temperature, dye-protein ratio, and molarity and type of buffer upon conjugation were studied. These technical factors were adjusted to produce conjugates for Corynebacterium diphtheriae which possessed higher specific titers than did reagents obtained by previously employed techniques.     

A mutation in the variable repeat region of the aggrecan gene (AGC1) causes a form of spondyloepiphyseal dysplasia associated with severe, premature osteoarthritis

Spondyloepiphyseal dysplasia (SED) encompasses a heterogeneous group of disorders characterized by shortening of the trunk and limbs. The autosomal dominant SED type Kimberley (SEDK) is associated with premature degenerative arthropathy and has been previously mapped in a multigenerational family to a novel locus on 15q26.1. This locus contains the gene AGC1, which encodes aggrecan, the core protein of the most abundant proteoglycan of cartilage. We screened AGC1 for mutations and identified a single-base-pair insertion, within the variable repeat region of exon 12 in affected individuals from the family with SEDK, that introduces a frameshift of 212 amino acids, including 22 cysteine residues, followed by a premature stop codon. This is the first identification of an AGC1 mutation causing a human disorder. This finding extends the spectrum of mutated genes that may cause SED and thus will aid in the molecular delineation of this complex group of conditions.