Graded deletion and virus-induced activation of autoreactive CD4+ T cells.
We have examined factors governing the negative selection of autoreactive CD4(+) T cells in transgenic mice expressing low (HA12 mice) vs. high (HA104 mice) amounts of the influenza virus hemagglutinin (HA). When mated with TS1 mice that express a transgenic TCR specific for the I-Ed-restricted determinant site 1 (S1) of HA, thymocytes expressing high levels of the clonotypic TCR were deleted in both HA-transgenic lineages. However, through allelic inclusion, thymocytes with lower levels of the clonotypic TCR evaded deletion in TS1 x HA12 and TS1 x HA104 mice to graded degrees. Moreover, in both lineages, peripheral CD4(+) T cells could be activated by the S1 peptide in vitro, and by influenza virus in vivo. These findings indicate that allelic inclusion can allow autoreactive CD4(+) thymocytes to evade thymic deletion to varying extents reflecting variation in the expression of the self peptide, and can provide a basis for the activation of autoreactive peripheral T cells by viruses bearing homologues of self peptides ("molecular mimicry").
Riley
M P
MP
The Wistar Institute, Philadelphia, PA 19104, USA.
Cerasoli
D M
DM
Jordan
M S
MS
Petrone
A L
AL
Shih
F F
FF
Caton
A J
AJ
D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation / Q000821:virology*; D002478:Cells, Cultured; D017637:Clonal Deletion / Q000276:immunology*; D002999:Clone Cells; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D009980:Influenza A virus / Q000276:immunology*; D007275:Injections, Intravenous; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology / Q000821:virology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010455:Peptides / Q000276:immunology / Q000494:pharmacology; D011948:Receptors, Antigen, T-Cell / Q000502:physiology
D018984:Epitopes, T-Lymphocyte; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D010455:Peptides; D011948:Receptors, Antigen, T-Cell