Mice deficient in perforin, CD4+ T cells, or CD28-mediated signaling maintain the typical immunodominance hierarchies of CD8+ T-cell responses to influenza virus.
CD8 T-cell (T(CD8+)) responses elicited by viral infection demonstrate the phenomenon of immunodominance: the numbers of T(CD8+) responding to different viral peptides vary over a wide range in a reproducible manner for individuals with the same major histocompatibility complex class I alleles. To better understand immunodominance, we examined T(CD8+) responses to multiple defined viral peptides following infection of mice with influenza virus. The immunodominance hierarchy of influenza virus-specific T(CD8+) was not greatly perturbed by the absence of either perforin or T-helper cells or by interference with B7 (CD80)-mediated signaling. These findings indicate that costimulation by antigen-presenting cells (APCs) or killing of APCs by T(CD8+) plays only a minor role in establishing the immunodominance hierarchy of antiviral T(CD8+) in this system. This points to intrinsic features of the T(CD8+) repertoire as major contributors to immunodominance.
Chen
Weisan
W
Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases/NIH, 4 Center Drive, Bethesda, MD 20892-0440, USA.
Bennink
Jack R
JR
Morton
Phillip A
PA
Yewdell
Jonathan W
JW
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D018122:B7-1 Antigen / Q000276:immunology*; D018106:CD28 Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology*; D009980:Influenza A virus / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D015398:Signal Transduction / Q000276:immunology*
D000956:Antigens, Viral; D018122:B7-1 Antigen; D018106:CD28 Antigens; D018984:Epitopes, T-Lymphocyte; D016056:Immunodominant Epitopes; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin