CD8(+) T lymphocytes (T(CD8)) responding to subdominant epitopes provide alternate targets for the immunotherapy of cancer, particularly when self-tolerance limits the response to immunodominant epitopes. However, the mechanisms that promote T(CD8) subdominance to tumor Ags remain obscure. We investigated the basis for the lack of priming against a subdominant tumor epitope following immunization of C57BL/6 (B6) mice with SV40 large tumor Ag (T Ag)-transformed cells. Immunization of B6 mice with wild-type T Ag-transformed cells primes T(CD8) specific for three immunodominant T Ag epitopes (epitopes I, II/III, and IV) but fails to induce T(CD8) specific for the subdominant T Ag epitope V. Using adoptively transferred T(CD8) from epitope V-specific TCR transgenic mice and immunization with T Ag-transformed cells, we demonstrate that the subdominant epitope V is weakly cross-presented relative to immunodominant epitopes derived from the same protein Ag. Priming of naive epitope V-specific TCR transgenic T(CD8) in B6 mice required cross-presentation by host APC. However, robust expansion of these T(CD8) required additional direct presentation of the subdominant epitope by T Ag-transformed cells and was only significant following immunization with T Ag-expressing cells lacking the immunodominant epitopes. These results indicate that limited cross-presentation coupled with competition by immunodominant epitope-specific T(CD8) contributes to the subdominant nature of a tumor-specific epitope. This finding has implications for vaccination strategies targeting T(CD8) responses to cancer.
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http://dx.doi.org/10.4049/jimmunol.175.2.700 | DOI Listing |
PLoS Negl Trop Dis
January 2025
Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, China.
Severe Fever with Thrombocytopenia Syndrome virus (SFTSV) is a novel identified pathogen, despite two decades of research on SFTSV, the potential widespread threats pose a significant challenge for researchers in developing new treatment and prevention methods. In this present, we have developed a multi-epitope mRNA vaccine for SFTSV and valid it with in silico methods. We screened 9 immunodominant epitopes for cytotoxic T cells (CTL), 7 for helper T cells (HTL), and 8 for Linear B-cell (LBL) based on promising candidate protein Gn, Gc, Np, and NSs.
View Article and Find Full Text PDFFront Immunol
January 2025
Adaptive Biotechnologies, Seattle, WA, United States.
Introduction: T cells are involved in the early identification and clearance of viral infections and also support the development of antibodies by B cells. This central role for T cells makes them a desirable target for assessing the immune response to SARS-CoV-2 infection.
Methods: Here, we combined two high-throughput immune profiling methods to create a quantitative picture of the T-cell response to SARS-CoV-2.
Microbiol Spectr
January 2025
Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical College, Institute of Pathogenic Biology, University of South China, Hengyang, China.
(Mp), a unique pathogen devoid of a cell wall, is naturally impervious to penicillin antibiotics. This bacterium is the causative agent of pneumonia, an acute pulmonary affliction marked by interstitial lung damage. Non-macrolide medications may have potential adverse effects on the developmental trajectory of children, thereby establishing macrolides as the preferred treatment for in pediatric patients.
View Article and Find Full Text PDFSARS-CoV-2 continues to evolve, with new variants emerging that evade pre-existing immunity and limit the efficacy of existing vaccines. One approach towards developing superior, variant-proof vaccines is to engineer immunogens that preferentially elicit antibodies with broad cross-reactivity against SARS-CoV-2 and its variants by targeting conserved epitopes on spike. The inner and outer faces of the Receptor Binding Domain (RBD) are two such conserved regions targeted by antibodies that recognize diverse human and animal coronaviruses.
View Article and Find Full Text PDFJ Nanobiotechnology
January 2025
State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, Discipline of Intelligent Instrument and Equipment, Department of Experimental Medicine, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, China.
The numerous high-risk carcinogenic types of human papillomavirus (HR-HPV) that lack vaccine protection underscore the urgent need to develop broader-spectrum HPV vaccines. This study addresses this need by focusing on HR-HPV types 53, 56, and 66, which are not currently targeted by existing vaccines. It introduces an effective method for their soluble expression, as well as that of their mutants, within an Escherichia coli expression system.
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