Cutting edge: the relative distribution of T cells responding to chemically dominant or minor epitopes of lysozyme is not affected by CD40-CD40 ligand and B7-CD28-CTLA-4 costimulatory pathways.
We examined the frequencies and specificities of the CD4+ T cell responses to the protein hen egg white lysozyme in mice deficient in the CD40-CD40 ligand or B7-CD28 costimulatory pathways. The frequency of T cells was decreased by between 3- and 4-fold in CD40-/- mice, and 12-fold in B7-1/B7-2-/- mice, but surprisingly, the relative distribution of T cells responding to peptides that were presented at levels that differed by >250-fold was similar. We also examined the CD4 response after blocking the regulatory molecule CTLA-4 during immunization. We observed no difference in either the frequency or specificity of the CD4+ T cell response if CTLA-4 was blocking during priming. Thus, the T cell response was generated toward the constellation of chemically dominant and subdominant epitopes as a whole, and did not discriminate among them based on their relative abundance.
DiPaolo
Richard J
RJ
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Unanue
Emil R
ER
D000069594:Abatacept; D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage; D017951:Antigen Presentation / Q000235:genetics; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology; D000943:Antigens, Differentiation / Q000276:immunology / Q000502:physiology*; D018122:B7-1 Antigen / Q000235:genetics / Q000502:physiology*; D051940:B7-2 Antigen; D018106:CD28 Antigens / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D019013:CD40 Antigens / Q000235:genetics / Q000502:physiology*; D023201:CD40 Ligand / Q000235:genetics / Q000502:physiology*; D060908:CTLA-4 Antigen; D002645:Chickens; D018920:Coculture Techniques; D018984:Epitopes, T-Lymphocyte / Q000276:immunology* / Q000378:metabolism; D006825:Hybridomas; D018796:Immunoconjugates; D016056:Immunodominant Epitopes / Q000276:immunology / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018655:Lymphocyte Count; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009113:Muramidase / Q000276:immunology* / Q000378:metabolism; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D019138:Antibodies, Blocking; D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; D019013:CD40 Antigens; D060908:CTLA-4 Antigen; C497965:Cd86 protein, mouse; C556707:Ctla4 protein, mouse; D018984:Epitopes, T-Lymphocyte; D018796:Immunoconjugates; D016056:Immunodominant Epitopes; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D023201:CD40 Ligand; D000069594:Abatacept; C421864:hen egg lysozyme; D009113:Muramidase