2,324 research outputs found
Vesicular stomatitis virus glycoprotein is necessary for H-2-restricted lysis of infected cells by cytotoxic T lymphocytes
Vesicular stomatitis virus (VSV) elicited cytotoxic thymus-derived lymphocytes (CTLs) in mice of the BALB/c and three congenic strains (BALB.b, BALB.k, BALB.HTG). CTL lysis of VSV-infected fibroblasts from the four strains was restricted by the target cells' major histocompatibility complex (H-2). Target cells were also infected with two temperature-sensitive mutants of VSV, tsM and tsG in which, respectively, the viral matrix protein and glycoprotein are not expressed at 39 degrees (restrictive temperature) on the infected cell's surface membrane. At the restrictive temperature, cells infected with wild-type VSV or tsM were lysed by CTLs, but cells infected with tsG were not. The requirement for the glycoprotein on the target cell was also evident from the ability of antisera to the glycoprotein to block completely CTL lysis of VSV-infected cells
Synthetic phospholipid vesicles containing a purified viral antigen and cell membrane proteins stimulate the development of cytotoxic T lymphocytes
Synthetic phospholipid vesicles (liposomes) containing the purified glycoprotein (G) of vesicular stomatitis virus (VSV) and solubilized membrane proteins from cells of the appropriate H-2 haplotype elicited H-2-restricted cytotoxic T lymphocytes (CTL) that lysed VSV-infected target cells. The CTL were elicited by intact liposomes, not by released components. Thus, when spleen cells from VSV-primed H-2d X H- 2b hybrid mice were stimulated with liposomes having G protein + membrane proteins from cells with one of the parental H-2 haplotypes, the resulting CTL lysed only VSV-infected target cells with that parent's H-2 type. This result argues against the view that T cells in general recognize only processed antigenic fragments on macrophages. Moreover, liposomes were only effective when G protein and cell membrane proteins were included in the same vesicles. This result suggests that for effective interaction with CTL precursors the antigen (G protein) and products of the H-2 complex must be closer to each other than 600-1,000 angstrom, the diameter of the lipid vesicles used in this study
Affinity Inequality among Serum Antibodies That Originate in Lymphoid Germinal Centers
Upon natural infection with pathogens or vaccination, antibodies are produced by a process called affinity maturation. As affinity maturation ensues, average affinity values between an antibody and ligand increase with time. Purified antibodies isolated from serum are invariably heterogeneous with respect to their affinity for the ligands they bind, whether macromolecular antigens or haptens (low molecular weight approximations of epitopes on antigens). However, less is known about how the extent of this heterogeneity evolves with time during affinity maturation. To shed light on this issue, we have taken advantage of previously published data from Eisen and Siskind (1964). Using the ratio of the strongest to the weakest binding subsets as a metric of heterogeneity (or affinity inequality), we analyzed antibodies isolated from individual serum samples. The ratios were initially as high as 50-fold, and decreased over a few weeks after a single injection of small antigen doses to around unity. This decrease in the effective heterogeneity of antibody affinities with time is consistent with Darwinian evolution in the strong selection limit. By contrast, neither the average affinity nor the heterogeneity evolves much with time for high doses of antigen, as competition between clones of the same affinity is minimal.Ragon Institute of MGH, MIT and HarvardSamsung Scholarship FoundationNational Science Foundation (U.S.). Graduate Research Fellowship (Grant 1122374
Gene Function Classification Using Bayesian Models with Hierarchy-Based Priors
We investigate the application of hierarchical classification schemes to the
annotation of gene function based on several characteristics of protein
sequences including phylogenic descriptors, sequence based attributes, and
predicted secondary structure. We discuss three Bayesian models and compare
their performance in terms of predictive accuracy. These models are the
ordinary multinomial logit (MNL) model, a hierarchical model based on a set of
nested MNL models, and a MNL model with a prior that introduces correlations
between the parameters for classes that are nearby in the hierarchy. We also
provide a new scheme for combining different sources of information. We use
these models to predict the functional class of Open Reading Frames (ORFs) from
the E. coli genome. The results from all three models show substantial
improvement over previous methods, which were based on the C5 algorithm. The
MNL model using a prior based on the hierarchy outperforms both the
non-hierarchical MNL model and the nested MNL model. In contrast to previous
attempts at combining these sources of information, our approach results in a
higher accuracy rate when compared to models that use each data source alone.
Together, these results show that gene function can be predicted with higher
accuracy than previously achieved, using Bayesian models that incorporate
suitable prior information
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