News & Views in 2002

The recent demonstration that T cells can recognize a single foreign pMHC complex suggests that TCR triggering does not require aggregation. Or does it?

The discovery of a V-like Ig multigene family in the protochordate amphioxus provides new insights into the evolution of the adaptive immune response.

Proteolytic cleavage generates the peptide repertoire displayed by MHC class I. Now, an interferon-γ–inducible aminopeptidase in the endoplasmic reticulum has been identified as the final player in this complex process.

Receptors in the immune system usually specialize in transmitting specific types of signals. However, by associating with two different signaling subunits, the receptor NKG2D can transmit distinct signals for either costimulation or full-fledged activation.

The source of Langerhans cells is controversial. New data show that the repopulation of these cells depends on how and to what extent, they are depleted from the skin.

CTLA-4–Ig is used to block the costimulation of T cells to interfere with their activation. This reagent may actually be working by provoking DCs to catabolize tryptophan, thereby depriving T cells and contributing to their demise.

Lipid second messengers are thought to be important in T cell activation. Two studies show the spatial-temporal organization of these lipids during immunological synapse formation and raise new questions about their functions.

A deficit of caspase-8 should presumably lead to over-activation of lymphocytes. A recent report in Nature from Lenardo's group, however, describes humans with a severe caspase-8 deficiency whose T cells, counter-intuitively, have impaired activation abilities.

Lymphocyte maturation and survival depend on a canonical NF-κB activation pathway. BAFF, however, uses an alternative NF-κB pathway to mediate signaling in maturing B cells.

DCs from different anatomical sites express distinct arrays of alternative HIV receptors. Some of these subsets could represent good gatekeepers, whereas others may be “Trojan horses” that carry HIV into the lymph node.

Apoptosis shapes T cell development and immune responses. The pro-apoptotic molecules Bax and Bak have overlapping essential functions in T cell development and homeostasis.

The complex interaction with APCs that is required for T cell activation is not well understood. A combination of experimental data and mathematical modeling provides insight into the competition between serial triggering and kinetic proofreading.

The existence of two distinct lineages of T_H1 cells may explain the relationship between activated effector T_H1 cells and long-term T_H1 memory cells.

AID burst onto the scene just a couple of years ago. For all of the progress, its actual mechanism for generating changes in DNA in B cells remains elusive.

NF-κB is important in many biological processes and is activated by ubiquitous protein kinases. However, in T cells, its activation is regulated by a specific set of adapter proteins.

T cell help is not obligatory for B cell Ig class switching. Instead, DC expression of BLyS and APRIL can provide the signals to induce T-independent B cell production of IgG and IgA.

“Cross-presentation” can prime CD8⁺ T cells. A transplantation system now reveals its role in destruction of the host endothelial cells that feed the graft.

FcεRI activation of mast cells was thought to be Lyn-dependent. It now appears that FcεRI also uses a Fyn kinase–dependent pathway that is essential for mast cell degranulation.

A role for Shc in T cell development was controversial. Two different genetic approaches now show Shc plays a nonredundant and essential function in pre-TCR signaling.

CD1b protein presents glycolipids of various tail lengths to T cells. The crystal structure of CD1b sheds light on its ability to accommodate these different glycolipids.