Innate immunity

Cutting edge: mast cell antimicrobial activity is mediated by expression of cathelicidin antimicrobial peptide. Di Nardo, A. et al. J. Immunol. 170, 2274–2278 (2003)

Cathelicidins are antimicrobial peptides that kill various microorganisms. The microbicidal activity of mast cells (MCs), together with the recent detection of cathelicidins in fish MCs, prompted Di Nardo et al. to investigate whether MCs in mice and humans contain cathelicidins. Human cathelicidin LL-37 was detected in skin MCs. Mice also have a single cathelicidin — CRAMP (cathelin-related antimicrobial peptide) — and this was detected in MCs. CRAMP expression was upregulated by mouse MCs following lipopolysaccharide stimulation. MCs from CRAMP-deficient mice had a reduced ability to kill group A streptococci.

MHC molecules

Functional expression of murine V2R pheromone receptors involves selective association with the M10 and M1 families of MHC class Ib molecules. Loconto, J. et al. Cell 112, 607–618 (2003)

Combinatorial coexpression of neural and immune multigene families in mouse vomeronasal sensory neurons. Ishii, T. et al. Curr. Biol. 13, 394–400 (2003)

Pheromones are chemical cues that trigger behaviours such as mating and territorial fighting. Two classes of pheromone receptor are expressed in the vomeronasal organ (VMO) — V1r in the apical layer and V2r in the basal layer. These studies show that V2r-expressing neurons in the basal layer also express non-classical MHC molecules (M1 and M10 families), and co-expression studies showed a correlation between the expression of a given V2r and a given M10 in a single cell. Immunoaffinity chromatography experiments showed that the V2r receptors are complexed with an M10 molecule plus β2-microglobulin. The complexes might function to regulate cell-surface expression of pheromone receptors. So, pheromone detection might involve MHC molecules.

Lymphocyte development

In vivo transposition mediated by V(D)J recombinase in human T lymphocytes. Messier, T. L. et al. EMBO J. 22, 1381–1388 (2003)

In addition to mediating the rearrangement of immunoglobulin and T-cell receptor (TCR) genes the recombination-activating gene (RAG) proteins have been shown, at least in vitro, to mediate transposition reactions, which could potentially lead to oncogenic events. This study provides the first evidence of RAG-mediated transposition in vivo. Human T cells with mutations in the HPRT (hypoxanthine-guanine phosphoribosyl transferase) gene were selected by culture with a cytotoxic purine analogue. Sequence analysis of two mutants indicated that insertions of a TCRα coding segment had occurred in intron 1 of HPRT. Subsequent breakpoint analysis showed the presence of TCRα signal ends, which is indicative of RAG-mediated transposition.