A single naturally processed measles virus peptide fully dominates the HLA-A*0201-associated peptide display and is mutated at its anchor position in persistent viral strains.
We studied the natural MHC class I display of measles virus (MV) epitopes. Peptide ligands associated with HLA-A*0201 were purified from a B lymphoblastoid cell line prior to and after infection with MV. Infection-induced peptides were revealed using microcapillary reversed phase high performance liquid chromatography electrospray ionization/mass spectrometry (microLC-ESI/MS) by subtraction of the "infected" and "uninfected" ion traces. Three naturally processed viral epitopes derived from different MV proteins were identified through tandem MS sequencing. These peptides were expressed at widely divergent levels of HLA-peptide complexes, but had similar binding capacities to HLA-A*0201. The most abundant viral peptide species, identified as residues 84-92 (KLWESPQEI) of the MV nonstructural C protein, was expressed at an unprecedented high density (> 10(5) copies per cell) and was immunogenic in HLA-A2/Kb-transgenic mice. Furthermore, natural mutants of this epitope, occurring in persistent lethal MV strains, were shown to have lost their HLA-A*0201 binding capacity. Thus, here we report for the first time the direct discovery through microLC-ESI/MS of a uniquely dominant viral HLA class I ligand, KLWESPQEI, with features eligible for immune selection pressure.
van Els
C A
CA
Laboratory of Vaccine Research, National Institute of Public Health and the Environment, Bilthoven, The Netherlands.
Herberts
C A
CA
van der Heeft
E
E
Poelen
M C
MC
van Gaans-van den Brink
J A
JA
van der Kooi
A
A
Hoogerhout
P
P
Jan ten Hove
G
G
Meiring
H D
HD
de Jong
A P
AP
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D000956:Antigens, Viral / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D015234:HLA-A Antigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D016056:Immunodominant Epitopes / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008024:Ligands; D013058:Mass Spectrometry; D008459:Measles virus / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics*; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011485:Protein Binding; D020539:Sequence Analysis, Protein; D013816:Thermodynamics; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D000956:Antigens, Viral; D015234:HLA-A Antigens; D016056:Immunodominant Epitopes; D008024:Ligands; D010446:Peptide Fragments; D017361:Viral Nonstructural Proteins