Asynchronous differentiation of CD8 T cells that recognize dominant and cryptic antigens.
Restriction of T cell responses to a few epitopes (immunodominance) is a central feature of immune responses. We analyzed the entire transcriptome of effector CD8 T cells specific for a dominant (H7(a)) and a cryptic (HY) mouse Ag and performed a longitudinal analysis of selected T cell differentiation markers. We found that Ag specificity had a relatively modest influence on the repertoire of genes that are transcriptionally modulated by the CD8 T cell differentiation program. Although the differentiation programs of anti-H7(a) and anti-HY T cells were similar, they did not progress simultaneously. The expansion peak of anti-H7(a) T cells was reached on day 10 while that of anti-HY T cells was attained on days 15-20. Between days 10 and 20, anti-H7(a) T cells were in the contraction phase and anti-HY T cells in the expansion phase. Furthermore, expansion and development of effector function were well-synchronized in anti-H7(a) T cells but were disconnected in anti-HY T cells. We propose that, by leading to selective expansion of the fittest CD8 T cells, immunodominance may be beneficial to the host. Inhibition of the T cell response to cryptic Ag would ensure that host resources (APC, cytokines) for which T cells compete are devoted to T cells with the best effector potential. One implication is that favoring expansion of the fittest effector T cells in general may be more important than increasing the diversity of the T cell repertoire.
Baron
Chantal
C
Institute of Research in Immunology and Cancer, University of Montreal, 6123 Succursale, Centreville, Montreal, Quebec, Canada;
Meunier
Marie-Christine
MC
Caron
Etienne
E
Côté
Caroline
C
Cameron
Mark J
MJ
Kelvin
David J
DJ
LeBlanc
Richard
R
Rineau
Vincent
V
Perreault
Claude
C
D000818:Animals; D000906:Antibodies; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology*; D049109:Cell Proliferation; D000939:Epitopes / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D006182:H-Y Antigen / Q000276:immunology; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D016056:Immunodominant Epitopes / Q000276:immunology*; D007700:Kinetics; D051379:Mice; D008815:Mice, Inbred Strains
D000906:Antibodies; D000939:Epitopes; D018984:Epitopes, T-Lymphocyte; D006182:H-Y Antigen; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D016056:Immunodominant Epitopes; C109963:hemagglutinin, avian influenza A virus