PMID- 26579122 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20151120 LR - 20181113 IS - 1664-3224 (Print) IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 6 DP - 2015 TI - Measles Virus Epitope Presentation by HLA: Novel Insights into Epitope Selection, Dominance, and Microvariation. PG - 546 LID - 10.3389/fimmu.2015.00546 [doi] LID - 546 AB - Immunity to infections with measles virus (MV) can involve vigorous human leukocyte antigen (HLA) class I-restricted CD8(+) cytotoxic T cell (CTL) responses. MV, albeit regarded monotypic, is known to undergo molecular evolution across its RNA genome. To address which regions of the MV proteome are eligible for recognition by CD8(+) CTLs and how different HLA class I loci contribute to the epitope display, we interrogated the naturally processed and presented MV peptidome extracted from cell lines expressing in total a broad panel of 16 different common HLA-A, -B, and -C molecules. The repertoire and abundance of MV peptides were bona fide identified by nanoHPLC-MS/MS. -Eighty-nine MV peptides were discovered and assignment to an HLA-A, -B, or -C allele, based on HLA-peptide affinity prediction, was in most cases successful. Length variation and presentation by multiple HLA class I molecules was common in the MV peptidome. More than twice as many unique MV epitopes were found to be restricted by HLA-B than by HLA-A, while MV peptides with supra-abundant expression rates (>5,000 cc) were rather associated with HLA-A and HLA-C. In total, 59 regions across the whole MV proteome were identified as targeted by HLA class I. Sequence coverage by epitopes was highest for internal proteins transcribed from the MV-P/V/C and -M genes and for hemagglutinin. At the genome level, the majority of the HLA class I-selected MV epitopes represented codons having a higher non-synonymous mutation rate than silent mutation rate, as established by comparison of a set of 58 unique full length MV genomes. Interestingly, more molecular variation was seen for the epitopes expressed at rates >/=1,000 cc. These data for the first time indicate that HLA class I broadly samples the MV proteome and that CTL pressure may contribute to the genomic evolution of MV. FAU - Schellens, Ingrid M AU - Schellens IM AD - Centre for Infectious Disease Control, National Institute for Public Health and the Environment , Bilthoven , Netherlands ; Laboratory of Translational Immunology, Department of Immunology, University Medical Center Utrecht , Utrecht , Netherlands ; Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht , Utrecht , Netherlands. FAU - Meiring, Hugo D AU - Meiring HD AD - Institute for Translational Vaccinology , Bilthoven , Netherlands. FAU - Hoof, Ilka AU - Hoof I AD - Theoretical Biology and Bioinformatics, Utrecht University , Utrecht , Netherlands. FAU - Spijkers, Sanne N AU - Spijkers SN AD - Centre for Infectious Disease Control, National Institute for Public Health and the Environment , Bilthoven , Netherlands ; Laboratory of Translational Immunology, Department of Immunology, University Medical Center Utrecht , Utrecht , Netherlands ; Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht , Utrecht , Netherlands. FAU - Poelen, Martien C M AU - Poelen MC AD - Centre for Infectious Disease Control, National Institute for Public Health and the Environment , Bilthoven , Netherlands. FAU - van Gaans-van den Brink, Jacqueline A M AU - van Gaans-van den Brink JA AD - Centre for Infectious Disease Control, National Institute for Public Health and the Environment , Bilthoven , Netherlands. FAU - Costa, Ana I AU - Costa AI AD - Laboratory of Translational Immunology, Department of Immunology, University Medical Center Utrecht , Utrecht , Netherlands ; Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht , Utrecht , Netherlands. FAU - Vennema, Harry AU - Vennema H AD - Centre for Infectious Disease Control, National Institute for Public Health and the Environment , Bilthoven , Netherlands. FAU - Kesmir, Can AU - Kesmir C AD - Theoretical Biology and Bioinformatics, Utrecht University , Utrecht , Netherlands. FAU - van Baarle, Debbie AU - van Baarle D AD - Centre for Infectious Disease Control, National Institute for Public Health and the Environment , Bilthoven , Netherlands ; Laboratory of Translational Immunology, Department of Immunology, University Medical Center Utrecht , Utrecht , Netherlands ; Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht , Utrecht , Netherlands. FAU - van Els, Cecile A C M AU - van Els CA AD - Centre for Infectious Disease Control, National Institute for Public Health and the Environment , Bilthoven , Netherlands. LA - eng PT - Journal Article DEP - 20151102 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 PMC - PMC4629467 OTO - NOTNLM OT - CD8 T cell epitope OT - HLA class I OT - HLA-A antigens OT - HLA-B antigens OT - HLA-C antigens OT - epitope mapping OT - immunodominance OT - measles virus EDAT- 2015/11/19 06:00 MHDA- 2015/11/19 06:01 PMCR- 2015/01/01 CRDT- 2015/11/19 06:00 PHST- 2015/08/12 00:00 [received] PHST- 2015/10/12 00:00 [accepted] PHST- 2015/11/19 06:00 [entrez] PHST- 2015/11/19 06:00 [pubmed] PHST- 2015/11/19 06:01 [medline] PHST- 2015/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2015.00546 [doi] PST - epublish SO - Front Immunol. 2015 Nov 2;6:546. doi: 10.3389/fimmu.2015.00546. eCollection 2015.