Browsing by Subject "antigen presentation"
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Item Open Access Mapping the SARS-CoV-2 spike glycoprotein-derived peptidome presented by HLA class II on dendritic cells.(Cell reports, 2021-05-13) Parker, Robert; Partridge, Thomas; Wormald, Catherine; Kawahara, Rebeca; Stalls, Victoria; Aggelakopoulou, Maria; Parker, Jimmy; Powell Doherty, Rebecca; Ariosa Morejon, Yoanna; Lee, Esther; Saunders, Kevin; Haynes, Barton F; Acharya, Priyamvada; Thaysen-Andersen, Morten; Borrow, Persephone; Ternette, NicolaUnderstanding and eliciting protective immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an urgent priority. To facilitate these objectives, we profile the repertoire of human leukocyte antigen class II (HLA-II)-bound peptides presented by HLA-DR diverse monocyte-derived dendritic cells pulsed with SARS-CoV-2 spike (S) protein. We identify 209 unique HLA-II-bound peptide sequences, many forming nested sets, which map to sites throughout S including glycosylated regions. Comparison of the glycosylation profile of the S protein to that of the HLA-II-bound S peptides reveals substantial trimming of glycan residues on the latter, likely induced during antigen processing. Our data also highlight the receptor-binding motif in S1 as a HLA-DR-binding peptide-rich region and identify S2-derived peptides with potential for targeting by cross-protective vaccine-elicited responses. Results from this study will aid analysis of CD4+ T cell responses in infected individuals and vaccine recipients and have application in next-generation vaccine design.Item Open Access Targeting Tumor-Associated Antigens in Hepatocellular Carcinoma for Immunotherapy: Past Pitfalls and Future Strategies.(Hepatology (Baltimore, Md.), 2020-08-07) Lu, Ligong; Jiang, Jun; Zhan, Meixiao; Zhang, Hui; Wang, Qian-Ting; Sun, Sheng-Nan; Guo, Xiao-Kai; Yin, Hua; Wei, Yadong; Li, Shi-You; Liu, Jun O; Li, Yong; He, You-WenThere are few treatment options for advanced-stage hepatocellular carcinoma (HCC). Targeting tumor-associated antigens (TAAs) for HCC immunotherapy has been tested clinically for many years with limited success. Recent advances in applying mutated tumor-specific neoantigens as immunotherapeutic targets raise hope that this class of antigens may be used in HCC treatment. Accordingly, multiple clinical trials have been initiated to test this concept. However, recent findings demonstrate that mutated neoantigens are rarely detected while unmutated antigens derived from TAAs are represented in the HLA ligandomes of HCC patients, suggesting a requirement to target TAAs for HCC immunotherapy. Herein, we review the potential pitfalls of previous clinical applications of targeting TAAs in HCC immunotherapy. Based on further understanding of the roles of different arms of adaptive immunity in antitumor immunity, we provide a perspective on how to address the unsatisfactory previous immunotherapy attempts in HCC. We propose a new vaccine platform that enhances all three arms of the adaptive immune system to improve TAA-based cancer vaccination in HCC patients. As many solid tumors with low and intermediate mutation burdens have similar TAA and neoantigen expression and presentation patterns, the new vaccine platform is broadly applicable. In conclusion, targeting TAA in HCC for immunotherapy is necessary and new strategies are needed to improve clinical efficacy.