Identifying broadly neutralizing antibodies against infectious agents such as influenza A viruses, HIV, and Plasmodium falciparum that display impressive degrees of antigenic variation is a major focus of investigators developing therapeutics and vaccines for pathogens of importance in public health (Corti and Lanzavecchia, 2013). In a previous post, I discussed one study (Klein et al., 2013) illustrating the sorts of unanticipated types of mutations found for broadly neutralizing antibodies against HIV. Lanzavecchia and colleagues have now identified antibodies reactive with antigens encoded by different isolates of Plasmodium falciparum and expressed on infected erythrocytes (Nature, 2015). They find an unexpected source for the heavy chain variable domain amino acid sequences that confer the broad anti-malarial reactivity against proteins in the RIFIN family.
Category: Immunology (Page 1 of 4)
It would be hard to identify an approach to cancer treatment that has received more attention recently than anti-checkpoint therapy (Pollack, 2015). This strategy for eliminating tumor cells is based on interfering with one or another pathway that inhibits the initial activation or functions of T cells, such as CD8+ cytotoxic T cells (CTL). Activated tumor-specific CTL can directly kill their targets. However, if copies of the T-cell surface molecule, PD-1, are bound by their physiological ligands on tumor cells, either PD-L1 or PD-L2, or other cells the ability of the T cell to perform its functions is substantially reduced. A report published in Science (2015) by Rizvi et al. last month addresses the question of whether tumor mutation burden correlates with response to anti-checkpoint therapy for non-small cell lung cancer (NSCLC).
Last month, Murphy and colleagues (Cell, 2015) published a fascinating report about a patient with an immunodeficiency syndrome that underwent spontaneous resolution. The mechanism for this remarkable outcome points to the importance of somatic cell selection and evolution in the origins, pathogenesis, and most dramatically in this case, elimination of disease.
Iron is a critical metal for essential cellular processes, such as respiration, in both human and microbial cells. Thus, in the context of infection, iron is a high-value cellular commodity and an evolutionist might reasonably expect a metallic tug-of-war between host and pathogen iron-binding proteins or other iron-binding molecules (siderophores). This speculation is impressively supported in a paper published this month (Barber and Elde, 2014). These authors provide strong evidence for positive selection affecting several sites in host (transferrin, Tf) and pathogen (transferrin binding protein A) iron-binding proteins based on a combination of genetic, structural, and functional experimental methods.
Epistasis refers to the influence of one genomic mutation or variant on the phenotypic effects of another mutation or variant. Based on available evidence and theory, this phenomenon has a major influence on evolutionary trajectories for organisms of all sorts. The role of epistasis has been studied primarily in the context of adaptive evolutionary change. In a recent paper (2014), Gong and Bloom attempt to determine the relative frequencies of epistatic interactions in adaptive versus stochastic evolution, i.e. evolution driven by selection as opposed to evolution resulting from random processes without a significant selective ‘pressure.’ Gong and Bloom perform this comparison by analyzing homologous nucleoprotein (NP) genes in human and swine influenza A viruses. The authors argue that the human viruses are subject to substantially more intense selection than the swine viruses since domestic swine are much shorter lived and their viruses are not as likely to be subjected to immune memory responses.