Cell migration

Role of CCR8 and other chemokine pathways in the migration of monocyte-derived dendritic cells to lymph nodes. Qu, C. et al. J. Exp. Med. 200, 1231–1241 (2004).

Monocytes can differentiate into either macrophages or lymph-node-homing dendritic cells (DCs); however, the events and molecules that are involved in monocyte fate are unclear. Although CCR2 is a key mediator of monocyte migration from the peritoneal cavity to the lymph nodes, in this study, the authors show that migration from the skin is CCR2 independent. In the skin, the GR1int mouse monocyte subpopulation readily differentiated into lymph-node-homing DCs and selectively expressed CCR7 and CCR8, which were both shown to be required for the emigration of these cells to the lymph nodes. CCR8 was also crucial for the migration of human monocyte-derived cells in a model of transendothelial trafficking, indicating a novel role for this chemokine in migration to lymph nodes.

Immunodeficiency

Severe combined immunodeficiency caused by deficiency in either the δ or ε subunit of CD3. De Sainte Basile, G. et al. J. Clin. Invest. 114, 1512–1517 (2004).

This study identifies the genetic defects in patients with a form of severe combined immunodeficiency (SCID) that is characterized by a complete defect of peripheral T cells but normal B cells and natural killer cells. The molecular bases of other forms of SCID include mutations in the genes that encode cytokine receptors, components of factors involved in the generation of antigen receptors, the phosphatase CD45 and the δ-chain of CD3. In this study, the authors show that mutations in the CD3δ or CD3ε gene that lead to a deficiency in expression of these CD3 chains are the basis for the disease. Absence of CD3δ was shown to cause a block in T-cell development at the intermediate stage of single-positive to double-positive transition.

Antigen processing

Unanticipated antigens: translation initiation at CUG with leucine. Schwab, S. R. et al. PLoS Biol. 2, 1774–1784 (2004).

Previous studies indicate that some MHC-class-I-bound peptides result from cryptic translation and that some of these peptides lack conventional AUG start codons. Schwab et al. investigated the mechanisms by which CUG functions as an initiation codon that encodes leucine. They found that the Kozak context of the CUG initiation codon influenced the efficiency with which it was decoded as leucine and that ribosomes specifically scan for the CUG initiation codon, indicating that CUG functions as a true initiation codon. However, the ribosomes that scan for CUG are probably distinct from those that scan for conventional AUG initiation codons, and these ribosomes use distinct factors to initiate translation, initiating translation with leucine independently of eukaryotic translation initiation factor 2α.