The murine cytomegalovirus immunomodulatory gene m152 prevents recognition of infected cells by M45-specific CTL but does not alter the immunodominance of the M45-specific CD8 T cell response in vivo.
Although in vitro studies have shown that herpesviruses, including murine CMV (MCMV), encode genes that interfere with the MHC class I pathway, their effects on the CTL response in vivo is unclear. We identified a D(b)-restricted CTL epitope from MCMV M45 by screening an MCMV genomic library using CTL clones isolated from mice infected with MCMV lacking m152. Because m152 severely inhibits CTL recognition of M45 in vitro, we questioned whether an M45-specific response would be generated in mice infected with wild-type MCMV expressing m152. Mice infected with wild-type MCMV or MCMVDelta(m)152 made similar responses to the M45 Ag. Moreover, we saw no skewing of the proportion of M45-specific CD8 T cells within the total MCMV-specific response after infection with MCMV with m152. Despite the profound effect m152 has on presentation of M45 in vitro, it does not affect the immunodominance of M45 in the CTL response in vivo.
Gold
Marielle C
MC
Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, OR 97201, USA.
Munks
Michael W
MW
Wagner
Markus
M
Koszinowski
Ulrich H
UH
Hill
Ann B
AB
Fling
Steven P
SP
D000276:Adjuvants, Immunologic / Q000235:genetics* / Q000502:physiology; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics*; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D002460:Cell Line; D002461:Cell Line, Transformed; D002469:Cell Separation; D002999:Clone Cells; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D006183:H-2 Antigens / Q000276:immunology; D006566:Herpesviridae Infections / Q000276:immunology; D064532:Histocompatibility Antigen H-2D; D017874:Immediate-Early Proteins / Q000235:genetics / Q000276:immunology; D016056:Immunodominant Epitopes / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018146:Muromegalovirus / Q000235:genetics* / Q000276:immunology* / Q000502:physiology; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D012264:Ribonucleotide Reductases / Q000276:immunology* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D014764:Viral Proteins
D000276:Adjuvants, Immunologic; D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D017874:Immediate-Early Proteins; D016056:Immunodominant Epitopes; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D014764:Viral Proteins; C044582:immediate-early proteins, cytomegalovirus; C104783:m152 protein, cytomegalovirus; D012264:Ribonucleotide Reductases; C422747:m45 protein, Mouse cytomegalovirus 1