@article{RitterZimmermannJoehrensetal.2018, author = {Ritter, Julia and Zimmermann, Karin and J{\"o}hrens, Korinna and Mende, Stefanie and Seegebarth, Anke and Siegmund, Britta and Hennig, Steffen and Todorova, Kremena and Rosenwald, Andreas and Daum, Severin and Hummel, Michael and Schumann, Michael}, title = {T-cell repertoires in refractory coeliac disease}, series = {Gut}, volume = {67}, journal = {Gut}, number = {4}, doi = {10.1136/gutjnl-2016-311816}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-226350}, pages = {644-653}, year = {2018}, abstract = {Objective Refractory coeliac disease (RCD) is a potentially hazardous complication of coeliac disease (CD). In contrast to RCD type I, RCD type II is a precursor entity of enteropathy-associated T-cell lymphoma (EATL), which is associated with clonally expanding T-cells that are also found in the sequentially developing EATL. Using high-throughput sequencing (HTS), we aimed to establish the small-intestinal T-cell repertoire (TCR) in CD and RCD to unravel the role of distinct T-cell clonotypes in RCD pathogenesis. Design DNA extracted from duodenal mucosa specimens of controls (n=9), active coeliacs (n=10), coeliacs on a gluten-free diet (n=9), RCD type I (n= 8), RCD type II (n= 8) and unclassified Marsh I cases (n= 3) collected from 2002 to 2013 was examined by TCR beta-complementarity- determining regions 3 (CDR3) multiplex PCR followed by HTS of the amplicons. Results On average, 106 sequence reads per sample were generated consisting of up to 900 individual TCR beta rearrangements. In RCD type II, the most frequent clonotypes (ie, sequence reads with identical CDR3) represent in average 42.6\% of all TCR beta rearrangements, which was significantly higher than in controls (6.8\%; p<0.01) or RCD type I (6.7\%; p<0.01). Repeat endoscopies in individual patients revealed stability of clonotypes for up to several years without clinical symptoms of EATL. Dominant clonotypes identified in individual patients with RCD type II were unique and not related between patients. CD-associated, gliad-independent CDR3 motifs were only detectable at low frequencies. Conclusions TCR beta-HTS analysis unravels the TCR in CD and allows detailed analysis of individual TCR beta rearrangements. Dominant TCR beta sequences identified in patients with RCD type II are unique and not homologous to known gliadin-specific TCR sequences, supporting the assumption that these clonal T-cells expand independent of gluten stimulation.}, language = {en} } @article{SinghVermaAkhoonetal.2016, author = {Singh, Krishna P. and Verma, Neeraj and Akhoon, Bashir A . and Bhatt, Vishal and Gupta, Shishir K. and Gupta, Shailendra K. and Smita, Suchi}, title = {Sequence-based approach for rapid identification of cross-clade CD8+ T-cell vaccine candidates from all high-risk HPV strains}, series = {3 Biotech}, volume = {6}, journal = {3 Biotech}, doi = {10.1007/s13205-015-0352-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-191056}, pages = {10}, year = {2016}, abstract = {Human papilloma virus (HPV) is the primary etiological agent responsible for cervical cancer in women. Although in total 16 high-risk HPV strains have been identified so far. Currently available commercial vaccines are designed by targeting mainly HPV16 and HPV18 viral strains as these are the most common strains associated with cervical cancer. Because of the high level of antigenic specificity of HPV capsid antigens, the currently available vaccines are not suitable to provide cross-protection from all other high-risk HPV strains. Due to increasing reports of cervical cancer cases from other HPV high-risk strains other than HPV16 and 18, it is crucial to design vaccine that generate reasonable CD8+ T-cell responses for possibly all the high-risk strains. With this aim, we have developed a computational workflow to identify conserved cross-clade CD8+ T-cell HPV vaccine candidates by considering E1, E2, E6 and E7 proteins from all the high-risk HPV strains. We have identified a set of 14 immunogenic conserved peptide fragments that are supposed to provide protection against infection from any of the high-risk HPV strains across globe.}, language = {en} }