Ir-gene control of T cell proliferative responses: two distinct expressions of the genetically nonresponsive state.
Two distinct modes of unresponsiveness to hen egg-white lysozyme (HEL) have been demonstrated in the "nonresponder" C57BL/10 Sn (B 10) mouse strain at the level of T cell proliferation. The first is an apparent inability to respond to a peptide of HEL comprising 70% of the molecule, LII (amino acids 13--105, when HEL is used as immunogen. On its own, LII is capable of eliciting a strong response from B 10 draining lymph node cells, but this capacity is concealed when the whole molecule is used for immunization (by suppressor cell activity raised against another part of HEL, as described by Adorini et al., J.Exp. Med. 1979. 150: 293). In the B 10.A mouse, LII and HEL are equally immunogenic. The second is an actual failure, presumably unrelated to suppression, to contrive a response to particular determinants on HEL, demonstrated for certain epitopes on LII and LIII (amino acids 106--129). Such a failure to respond was maintained despite an increase in the immunizing dose of peptide to a molarity at which HEL itself could overcome Ir gene control. B 10 cells responding to a high dose of HEL, or to the immunogenic lysozyme from ring-neck pheasant, were also unable to respond to these epitopes. These deficits in responsiveness appear to be characteristic manifestations of the relevant haplotype of the major histocompatibility complex. They may not only reflect the balance between competing T cell subpopulations, but also the constraints of associative recognition that may underlie the presentation of particular antigenic specificities.
D000818:Animals; D000917:Antibody Formation; D000918:Antibody Specificity; D002455:Cell Division; D002645:Chickens; D004306:Dose-Response Relationship, Immunologic; D004529:Egg White; D005260:Female; D005802:Genes, MHC Class II; D007108:Immune Tolerance; D051379:Mice; D008810:Mice, Inbred C57BL / Q000235:genetics*; D009113:Muramidase / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology*
D009113:Muramidase