The immunodominance effect, whereby the presence of immunodominant epitopes prevents recognition of nondominant determinants presented on the same antigen-presenting cell (APC) considerably restricts the repertoire of cytotoxic T lymphocyte (CTL) responses. To elucidate the molecular basis of the immunodominance effect, we compared the interactions of a dominant (B6(dom1)) and a nondominant epi...

Although immunodominance of CD8(+) T-cell responses is a well-recognised feature of viral infections, its role in responses to more antigenically complex pathogens is less clear. In previous studies we have observed that CD8(+) T-cell responses to Theileria parva exhibit different patterns of parasite strain specificity in cattle of different MHC genotypes. In the current study, we demonstrated...

To evaluate the impact of sustained viral loads on anti-viral T cell responses we compared responses that cleared acute lymphocytic choriomeningitis virus infection with those that were elicited but could not resolve chronic infection. During acute infection, as replicating virus was cleared, CD8 T cell responses were down-regulated, and a pool of resting memory cells developed. In chronically ...

Understanding immunity to vaccinia virus (VACV) is important for the development of safer vaccines for smallpox- and poxvirus-vectored recombinant vaccines. VACV is also emerging as an outstanding model for studying CD8(+) T cell immunodominance because of the large number of CD8(+) T cell epitopes known for this virus in both mice and humans. In this study, we characterize the CD8(+) T cell re...

In an effort to develop an AIDS vaccine that elicits high-frequency cytotoxic-T-lymphocyte (CTL) responses with specificity for a diversity of viral epitopes, we explored two prototype multiepitope plasmid DNA vaccines in the simian-human immunodeficiency virus/rhesus monkey model to determine their efficiency in priming for such immune responses. While a simple multiepitope vaccine construct d...

CD8 T cell responses against different tumor neoantigens occur simultaneously, yet little is known about their interplay and its impact on function control. In mouse lung adenocarcinoma, we find that immunodominance established in tumors, wherein expansion predominantly driven by the antigen most stably binds MHC. T cells responding to subdominant antigens are enriched for a TCF1+ progenitor ph...

Primary CD8+ T cell responses play a major role in controlling infection by many viruses, and CD8+ memory T cells can confer immunity to virus challenge. In this study we report that for many epitope-specific CD8+ T cell populations, the regulation of an important effector molecule, IFN-gamma, changes dramatically over the course of infection. During the acute phase of infection, many CD8+ T ce...

The outer capsid proteins VP4 and VP7 of group A rotaviruses are both targets of neutralizing antibody produced following natural infection in humans. Of interest is the relative importance and immunodominance of each protein in the generation of a protective immune response. In order to measure neutralizing antibody responses to VP4 and VP7 separately, reassortants bearing VP4 of each of the m...

The current understanding of antigenic escape dynamics is based on models with single epitopes. The usual idea is that a mutation which enables a pathogen (virus, bacteria, etc) to escape from a given immune response confers a selective advantage. The "escape mutant" may then increase in abundance until it induces a new specific response against itself. In this paper a new picture is developed,...

Human CMV establishes a lifelong latent infection in the majority of people worldwide. Although most infections are asymptomatic, immunocompetent hosts devote an extraordinary amount of immune resources to virus control. To increase our understanding of CMV immunobiology in an animal model, we used a genomic approach to comprehensively map the C57BL/6 CD8 T cell response to murine CMV (MCMV). R...