Selection for escape mutant immunodeficiency viruses by cytotoxic T lymphocytes (CTL) has been well characterized and may be associated with disease progression. CTL epitopes accrue escape mutations at different rates in vivo. Interestingly, certain high-frequency CTL do not select for escape until the chronic phase of infection. Here we show that mutations conferring escape from immunodominant CTL directed against an epitope in the viral Gag protein are strongly associated with extraepitopic mutations in gag in vivo. The extraepitopic mutations partially restore in vitro replicative fitness of viruses bearing the escape mutations. Constraints on epitope sequences may therefore play a role in determining the rate of escape from CTL responses in vivo.

A study has been conducted of the effects of deposition conditions on the radiation hardness of borophosphosilicate glass (BPSG). Films deposited by two common deposition techniques were evaluated using gamma cell testing, electron spin resonance (ESR), and capacitance voltage (CV) measurements. The results indicate that two stoichiometrically similar films can differ greatly in radiation tolerance depending on the deposition conditions.

We report a comparison of CO and NO emissions from dimethyl ether (DME), propane, and n-butane laminar premixed flames. Measurements were made with a water-cooled stainless steel sampling probe situated above the visible reaction zone of a co-flow burner. Species were measured by a Nicolet Magna 550 FTIR spectrometer. The fuels were compared on the basis of constant mass flow, constant C-atom flow, and constant firing rate. Results were corrected for dilution by entrained air. Our results indicate that on all bases considered, DME demonstrated lower CO emission than propane and n-butane over a broad range of stoichiometries. NO production from DME was generally less than or similar to propane and n-butane over the same stoichiometric range. We conclude that in terms of its relative CO and NO production, DME is a viable alternative utility fuel.

Diseases due to fungi represent a growing public health problem that demand new treatments and methods of vaccine prevention (8). The rational design of vaccines against fungi requires an understanding of the elements of antifungal immunity. Cellular immunity is pivotal in acquired resistance to fungal infections and is organized into clonal populations of antigen (Ag)-specific CD4 ϩ T cells (8,30,40). The ability to track, enumerate, and characterize Ag-specific T cells precisely requires knowledge of the Ag peptide. With such information, peptide-major histocompatibility complex (MHC) tetramers and T cell receptor (TCR) transgenic (Tg) mice have been used to track and enumerate Ag-specific T cells ex vivo to circumvent in vitro expansion or distortion of immune responses.Reagents are available to precisely study T cell immunity with model agents such as lymphocytic choriomeningitis virus and Listeria (9, 22), but the study of most other pathogens is not readily approachable with these high-resolution methods. For the systemic dimorphic fungi, no T cell Ag epitopes have been elucidated to provide the tools to address this gap in knowledge. To bridge this gap, we engineered heterologous Ag and epitopes into a vaccine strain of a pathogenic fungus to let us induce, track, quantify, characterize, and functionally analyze adoptively transferred TCR Tg T cells specific for the foreign Ag in vaccinated animals.Blastomycosis is a systemic infection due to the dimorphic fungus Blastomyces dermatitidis. We have created a live attenuated vaccine against lethal experimental infection (38). The vaccine induces sterilizing immunity that is mediated by CD4 ϩ T cells, although the protective antigen remains unknown. Still, this model and the potent activity of these CD4 ϩ T cells offer the chance to elucidate the requirements for inducing and maintaining antifungal CD4 ϩ T cells by vaccination. As a surrogate means to study the in vivo activation, proliferation, and maintenance of Blastomyces-specific CD4 ϩ T cells, we expressed model epitopes on the vaccine B. dermatitidis yeast using BAD1, an abundant surface protein, as a carrier. Yeast surface Ag display is thought to be one feature that promotes the generation of antifungal immune responses.In other nonfungal models, the availability of Ag and the number of naïve T cell precursors in a host can affect the priming and development of CD4 ϩ effector and memory T cells (1, 27). However, little is known about the identity, cellular distribution, and expression levels of fungal T cell epitopes and how these factors influence the development of antifungal immunity. We report that expressing a model epitope such as E␣ peptide on vaccine yeast induced the activation and proliferation of corresponding naïve, adoptively transferred TCR Tg TEa cells. We describe the experimental system and our results enabling the tracking of fungal Ag presentation to CD4 ϩ T cells and the corresponding Agspecific T cell response during their earliest stages of activation, proliferation, and expansi...