Immunology today最新文献

The histories of monoclonal antibodies and the fluorescence activated cell sorter (FACS) are as closely intertwined as their current uses in biology and medicine. Here, Leonore Herzenberg, Stephen De Rosa and Leonard Herzenberg recount the meeting and the mating of these two technologies, whose offspring now populate clinical and research laboratories throughout the world.

Thousands of mouse monoclonal antibodies have been produced from hybridomas over the past 25 years. The same technique can now be used to clone human antibodies from transgenic mice. Full-length antibodies and recombinant fragments engineered for various diagnostic and therapeutic applications can be obtained in reasonably large amounts after expression in mammalian cells, milk and plants.

The antiglobulin response is perceived as a major problem in the clinical development of therapeutic antibodies. Successive technical developments such as chimeric, humanized and, now, fully human antibodies claim to offer improved solutions to this problem. Although there is clear evidence that chimeric antibodies are less immunogenic than murine monoclonal antibodies, little evidence exists to support claims for further improvements as a result of more elaborate humanization protocols.

Current theories of T-cell migration are essentially ‘template’ or ‘instructional’ models of lymphocyte homing. However, like antigen specificity, lymphocyte homing may be based on clonal selection from a diverse repertoire of homing specificities.

As mice are often used to model human major histocompatibility complex (MHC)-associated diseases, it is important to understand how their MHC regions differ at the DNA level. The sequencing of the mouse MHC (H2 region) has enabled a detailed map of this region to be assembled for comparison with the human MHC. Here, Richard Allcock and colleagues outline the similarities between the human and mouse MHC regions and discuss notable differences that might affect disease models.

Given the importance of responding to infections with the right defensive strategy, much interest has focused on cytokine differentiation in CD4⁺ T cells. However, relatively little is known of the logistics of T-cell help for B cells. Here, Lucy Walker and colleagues propose key roles for CD28 and OX40 in coordinating the selection, expansion and migration of CD4⁺ T cells to B-cell follicles.

The majority of expanded T cells generated during an immune response are cleared by apoptosis. Prevention of death in some activated T cells enables the persistence of a memory T-cell pool. Here, observations that IFN-α and IFN-β inhibit activated T-cell apoptosis are described. Although this enables memory T cells to persist without antigen, excessive IFN-α or IFN-γ secretion might lead to chronic inflammation.

Recent NMR analyses of IgG–FcγR interactions in solution have identified the FcγR-binding site on the Fc region and provided evidence for a conformational change in the Fc occurring during the interaction. Here, Koichi Kato and colleagues discuss how this conformational change explains the incapacity of IgG molecules to trigger responses deleterious to the organism, in the absence of antigen cross-linking.

The wide-ranging effects of interleukin 18 as a regulator of innate and acquired immune responses, and particularly its role in human autoimmune diseases, suggest its potential importance as a therapeutic target.