Impact of distinct poxvirus infections on the specificities and functionalities of CD4+ T cell responses.

UNLABELLED: The factors that determine CD4+ T cell (TCD4+) specificities, functional capacity, and memory persistence in response to complex pathogens remain unclear. We explored these parameters in the C57BL/6 mouse through comparison of two highly related (\u3e92% homology) poxviruses: ectromelia virus (ECTV), a natural mouse pathogen, and vaccinia virus (VACV), a heterologous virus that nevertheless elicits potent immune responses. In addition to elucidating several previously unidentified major histocompatibility complex class II (MHC-II)-restricted epitopes, we observed many qualitative and quantitative differences between the TCD4+ repertoires, including responses not elicited by VACV despite complete sequence conservation. In addition, we observed functional heterogeneity between ECTV- and VACV-specific TCD4+ at both a global and individual epitope level, particularly greater expression of the cytolytic marker CD107a from TCD4+ following ECTV infection. Most striking were differences during the late memory phase where, in contrast to ECTV, VACV infection failed to elicit measurable epitope-specific TCD4+ as determined by intracellular cytokine staining. These findings illustrate the strong influence of epitope-extrinsic factors on TCD4+ responses and memory. IMPORTANCE: Much of our understanding concerning host-pathogen relationships in the context of poxvirus infections stems from studies of VACV in mice. However, VACV is not a natural mouse pathogen, and therefore, the relevance of results obtained using this model may be limited. Here, we explored the MHC class II-restricted TCD4+ repertoire induced by mousepox (ECTV) infection and the functional profile of the responding epitope-specific TCD4+, comparing these results to those induced by VACV infection under matched conditions. Despite a high degree of homology between the two viruses, we observed distinct specificity and functional profiles of TCD4+ responses at both acute and memory time points, with VACV-specific TCD4+ memory being notably compromised. These data offer insight into the impact of epitope-extrinsic factors on the resulting TCD4+ responses

Private education in Crimea in the 19th-early 20th centuries: background, foundation, structure

The social development process taking place in Russian Federation, the development of new democratic society and its integration into the world and European cultural and educational space have led to an active innovational increase of pedagogical concept and experience, the example of which is represented by private education. The situation in the sphere of education development, determined by directive public administration rejection, the latest configurations of social and educational interaction construction determined the necessity to study the private secondary educational institutions foundation process within the educational reform and its integration into the national education system.</jats:p

Two T Cell Epitopes from the M5 Protein of Viable <i>Streptococcus pyogenes</i> Engage Different Pathways of Bacterial Antigen Processing in Mouse Macrophages

Abstract We studied the mechanisms of MHC class II-restricted bacterial Ag processing of the surface fibrillar M5 protein from viable Streptococcus pyogenes in murine macrophages. Two previously defined T cell epitopes were studied using T cell hybridomas specific for 308–319/Ad, associated with the cell wall on the surface of streptococci, and 17–31/Ed, located at the protruding amino terminus of M5. Studies with metabolic inhibitors showed that slow (1 h) processing of M5 308–319 occurred in late endosomes and was dependent on newly synthesized MHC class II molecules and microtubules and on communications between early and late endosomes, consistent with engagement of the classical MHC class II processing pathway. In contrast, fast (15 min) bacterial Ag processing of 17–31 occurred in early endosomes independently of newly synthesized MHC class II molecules and microtubules and of trafficking between early and late endosomes, consistent with the recycling MHC class II processing pathway. Finally, bacterial Ag processing of the epitopes exhibited differential sensitivity to blocking with anti-MHC class II Abs. Thus, two T cell epitopes of a single protective Ag from the surface of whole bacteria are routed to distinct MHC class II processing pathways.</jats:p

Private education in Crimea in the 19th-early 20th centuries: background, foundation, structure

The social development process taking place in Russian Federation, the development of new democratic society and its integration into the world and European cultural and educational space have led to an active innovational increase of pedagogical concept and experience, the example of which is represented by private education. The situation in the sphere of education development, determined by directive public administration rejection, the latest configurations of social and educational interaction construction determined the necessity to study the private secondary educational institutions foundation process within the educational reform and its integration into the national education system