Autoreactivity against induced or upregulated abundant self-peptides in HLA-A*0201 following measles virus infection.
Infectious agents have been implied as causative environmental factors in the development of autoimmunity. However, the exact nature of their involvement remains unknown. We describe a possible mechanism for the activation of autoreactive T cells induced by measles virus (MV) infection. The display of HLA-A*0201 associated peptides obtained from MV infected cells was compared with that from uninfected cells by mass spectrometry. We identified two abundant self peptides, IFI-6-16(74-82) and Hsp90beta(570-578), that were induced or upregulated, respectively, following infection. Their parental proteins, the type I interferon inducible protein IFI-6-16, and the beta chain of heat shock protein 90, have not been involved in MV pathogenesis. MV infection caused minor and major changes in the intracellular expression patterns of these proteins, possibly leading to altered peptide processing. CD8+ T cells capable of recognizing the self-peptides in the context of HLA-A*0201 were detectable at low basal levels in the neonatal and adult human T cell repertoire, but were functionally silent. In contrast, peptide-specific producing IFN-gamma producing effector cells were present in MV patients during acute infection. Thus, MV infection induces an enhanced display of self-peptides in MHC class I, which may lead to the temporary activation of autoreactive T cells.
Herberts
Carla A
CA
Laboratory of Vaccine Research, National Institute of Public Health and the Environment, Bilthoven, The Netherlands.
van Gaans-van den Brink
Jacqueline
J
van der Heeft
Ed
E
van Wijk
Margot
M
Hoekman
Jan
J
Jaye
Assan
A
Poelen
Martien C M
MC
Boog
Claire J P
CJ
Roholl
Paul J M
PJ
Whittle
Hilton
H
de Jong
Ad P J M
AP
van Els
Cécile A C M
CA
D000328:Adult; D000818:Animals; D001324:Autoantigens / Q000378:metabolism*; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D015234:HLA-A Antigens / Q000276:immunology*; D015789:HLA-A2 Antigen; D018841:HSP90 Heat-Shock Proteins / Q000276:immunology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000821:virology; D008457:Measles / Q000276:immunology* / Q000821:virology; D008459:Measles virus / Q000235:genetics / Q000276:immunology*; D015854:Up-Regulation; D014709:Vero Cells
D001324:Autoantigens; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D018841:HSP90 Heat-Shock Proteins