Dynamics of measles virus protein expression are reflected in the MHC class I epitope display.
Following measles virus (MV) infection, viral peptides are presented to CTL by MHC class I molecules on infected antigen presenting cells at widely different epitope densities. Whereas three MV epitopes (MV-M(211-219), MV-F(438-446) and MV-H(30-38)) derived from different structural proteins occur at regular densities, one peptide derived from the non-structural C protein (MV-C(84-92)) fully dominates the MV peptide display in HLA class I molecules on end-stage-infected human B cells. Here we demonstrate that this hierarchy in MV epitope density is not a constant, but varies with progression of infection. While MV-M(211-219), MV-F(438-446) and MV-H(30-38) epitopes were already presented by HLA class I molecules early in infection, expression of MV-C(84-92) was restricted to the later phases of infection. These dynamics in epitope densities correlated with features of MV protein expression. Synthesis of C protein mainly focused towards the final stages of infection, while the other MV proteins were more readily synthesised from earlier time points on, in line with the emergence of their respective epitopes. Furthermore, the most abundant MV epitope was derived from the most unstable viral protein and vice versa, suggesting that the stability of viral proteins may be an indicator for the final abundance of their epitopes. Thus, even though many other factors may influence the generation of peptide-MHC class I complexes, we here report that the regulation of viral protein expression seems closely linked to the viral MHC class I epitope display. Finally, the observed dynamics in viral epitope hierarchy may have important implications for the induction of antiviral T cell immunity.
Herberts
Carla A
CA
Laboratory of Vaccine Research, National Institute of Public Health and the Environment, P.O. Box 1, 3720 BA Bilthoven, The Netherlands.
Meiring
Hugo M
HM
van Gaans-van den Brink
Jacqueline A M
JA
van der Heeft
Ed
E
Poelen
Martien C M
MC
Boog
Claire J P
CJ
de Jong
Ad P J M
AP
van Els
Cécile A C M
CA
D017951:Antigen Presentation / Q000276:immunology*; D000956:Antigens, Viral / Q000096:biosynthesis / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology / Q000821:virology; D018985:Epitopes, B-Lymphocyte / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D008457:Measles / Q000276:immunology* / Q000821:virology; D008459:Measles virus / Q000235:genetics / Q000276:immunology*; D014779:Virus Replication / Q000276:immunology
D000956:Antigens, Viral; D018985:Epitopes, B-Lymphocyte; D015395:Histocompatibility Antigens Class I