PMID- 23280567 OWN - NLM STAT- MEDLINE DCOM- 20130612 LR - 20221207 IS - 1521-4141 (Electronic) IS - 0014-2980 (Print) IS - 0014-2980 (Linking) VI - 43 IP - 4 DP - 2013 Apr TI - Conditional ligands for Asian HLA variants facilitate the definition of CD8+ T-cell responses in acute and chronic viral diseases. PG - 1109-20 LID - 10.1002/eji.201243088 [doi] AB - Conditional ligands have enabled the high-throughput production of human leukocyte antigen (HLA) libraries that present defined peptides. Immunomonitoring platforms typically concentrate on restriction elements associated with European ancestry, and such tools are scarce for Asian HLA variants. We report 30 novel irradiation-sensitive ligands, specifically targeting South East Asian populations, which provide 93, 63, and 79% coverage for HLA-A, -B, and -C, respectively. Unique ligands for all 16 HLA types were constructed to provide the desired soluble HLA product in sufficient yield. Peptide exchange was accomplished for all variants as demonstrated by an ELISA-based MHC stability assay. HLA tetramers with redirected specificity could detect antigen-specific CD8(+) T-cell responses against human cytomegalovirus, hepatitis B (HBV), dengue virus (DENV), and Epstein-Barr virus (EBV) infections. The potential of this population-centric HLA library was demonstrated with the characterization of seven novel T-cell epitopes from severe acute respiratory syndrome coronavirus, HBV, and DENV. Posthoc analysis revealed that the majority of responses would be more readily identified by our unbiased discovery approach than through the application of state-of-the-art epitope prediction. This flow cytometry-based technology therefore holds considerable promise for monitoring clinically relevant antigen-specific T-cell responses in populations of distinct ethnicity. CI - (c) 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. FAU - Chang, Cynthia X L AU - Chang CX AD - Department of Microbiology, National University of Singapore, Singapore. FAU - Tan, Anthony T AU - Tan AT FAU - Or, Ming Yan AU - Or MY FAU - Toh, Kai Yee AU - Toh KY FAU - Lim, Pei Yiing AU - Lim PY FAU - Chia, Adeline S E AU - Chia AS FAU - Froesig, Thomas M AU - Froesig TM FAU - Nadua, Karen D AU - Nadua KD FAU - Oh, Hsueh-Ling J AU - Oh HL FAU - Leong, Hoe Nam AU - Leong HN FAU - Hadrup, Sine R AU - Hadrup SR FAU - Gehring, Adam J AU - Gehring AJ FAU - Tan, Yee-Joo AU - Tan YJ FAU - Bertoletti, Antonio AU - Bertoletti A FAU - Grotenbreg, Gijsbert M AU - Grotenbreg GM LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130214 PL - Germany TA - Eur J Immunol JT - European journal of immunology JID - 1273201 RN - 0 (Epitopes, T-Lymphocyte) RN - 0 (HLA Antigens) RN - 0 (Ligands) RN - 0 (Peptides) SB - IM MH - Amino Acid Sequence MH - *Asian People MH - CD8-Positive T-Lymphocytes/*immunology MH - Epitopes, T-Lymphocyte/chemistry/*immunology MH - HLA Antigens/chemistry/genetics/*immunology MH - Humans MH - Ligands MH - Molecular Sequence Data MH - Peptides/chemistry/immunology MH - Protein Multimerization MH - Protein Stability MH - Virus Diseases/*immunology PMC - PMC3655610 COIS- The authors declare no financial or commercial conflict of interest. EDAT- 2013/01/03 06:00 MHDA- 2013/06/13 06:00 PMCR- 2020/04/17 CRDT- 2013/01/03 06:00 PHST- 2012/10/24 00:00 [received] PHST- 2012/12/07 00:00 [revised] PHST- 2012/12/21 00:00 [accepted] PHST- 2013/01/03 06:00 [entrez] PHST- 2013/01/03 06:00 [pubmed] PHST- 2013/06/13 06:00 [medline] PHST- 2020/04/17 00:00 [pmc-release] AID - EJI2543 [pii] AID - 10.1002/eji.201243088 [doi] PST - ppublish SO - Eur J Immunol. 2013 Apr;43(4):1109-20. doi: 10.1002/eji.201243088. Epub 2013 Feb 14.