PMID- 23748502 OWN - NLM STAT- MEDLINE DCOM- 20140213 LR - 20220318 IS - 1546-1696 (Electronic) IS - 1087-0156 (Print) IS - 1087-0156 (Linking) VI - 31 IP - 7 DP - 2013 Jul TI - Combinatorial tetramer staining and mass cytometry analysis facilitate T-cell epitope mapping and characterization. PG - 623-9 LID - 10.1038/nbt.2593 [doi] AB - It is currently not possible to predict which epitopes will be recognized by T cells in different individuals. This is a barrier to the thorough analysis and understanding of T-cell responses after vaccination or infection. Here, by combining mass cytometry with combinatorial peptide-MHC tetramer staining, we have developed a method allowing the rapid and simultaneous identification and characterization of T cells specific for many epitopes. We use this to screen up to 109 different peptide-MHC tetramers in a single human blood sample, while still retaining at least 23 labels to analyze other markers of T-cell phenotype and function. Among 77 candidate rotavirus epitopes, we identified six T-cell epitopes restricted to human leukocyte antigen (HLA)-A*0201 in the blood of healthy individuals. T cells specific for epitopes in the rotavirus VP3 protein displayed a distinct phenotype and were present at high frequencies in intestinal epithelium. This approach should be useful for the comprehensive analysis of T-cell responses to infectious diseases or vaccines. FAU - Newell, Evan W AU - Newell EW AD - Agency for Science, Technology and Research, Singapore Immunology Network, Singapore. evan_newell@immunol.a-star.edu.sg FAU - Sigal, Natalia AU - Sigal N FAU - Nair, Nitya AU - Nair N FAU - Kidd, Brian A AU - Kidd BA FAU - Greenberg, Harry B AU - Greenberg HB FAU - Davis, Mark M AU - Davis MM LA - eng GR - R01 AI021362/AI/NIAID NIH HHS/United States GR - U19-AI090019/AI/NIAID NIH HHS/United States GR - U19 AI090019/AI/NIAID NIH HHS/United States GR - U19-AI057229/AI/NIAID NIH HHS/United States GR - HHMI/Howard Hughes Medical Institute/United States GR - U19 AI057229/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20130609 PL - United States TA - Nat Biotechnol JT - Nature biotechnology JID - 9604648 RN - 0 (Antigens, Viral) RN - 0 (Epitopes, T-Lymphocyte) RN - 0 (HLA-A Antigens) RN - 0 (Histocompatibility Antigens Class I) RN - 0 (Histocompatibility Antigens Class II) RN - 0 (Peptides) SB - IM CIN - Nat Biotechnol. 2013 Jul;31(7):609-10. PMID: 23839145 MH - Antigens, Viral/immunology MH - *Epitope Mapping MH - Epitopes, T-Lymphocyte/*immunology MH - Flow Cytometry MH - HLA-A Antigens/*immunology MH - Histocompatibility Antigens Class I/immunology MH - Histocompatibility Antigens Class II/immunology MH - Humans MH - Mass Spectrometry MH - Peptides/chemistry/*immunology MH - Rotavirus/immunology/metabolism MH - T-Lymphocytes PMC - PMC3796952 MID - NIHMS501485 EDAT- 2013/06/12 06:00 MHDA- 2014/02/14 06:00 PMCR- 2013/10/15 CRDT- 2013/06/11 06:00 PHST- 2013/02/07 00:00 [received] PHST- 2013/04/22 00:00 [accepted] PHST- 2013/06/11 06:00 [entrez] PHST- 2013/06/12 06:00 [pubmed] PHST- 2014/02/14 06:00 [medline] PHST- 2013/10/15 00:00 [pmc-release] AID - nbt.2593 [pii] AID - 10.1038/nbt.2593 [doi] PST - ppublish SO - Nat Biotechnol. 2013 Jul;31(7):623-9. doi: 10.1038/nbt.2593. Epub 2013 Jun 9.