MHC genotype controls the capacity of ligand density to switch T helper (Th)-1/Th-2 priming in vivo.
A quantitative mechanism for the differentiation of CD4 T cells into recognized subsets of Th1 and Th2 effectors is controversial. Here, we define the Ag dose more precisely to the density of a minimal immunogenic peptide presented on the surface of a specific APC type. Th1 and Th2 responder MHC genotypes differ by as much as an order of magnitude in the density of this peptide displayed on B7-2+ B cells. We asked whether such B cells presenting a low ligand density primed Th2 effectors in an MHC genotype with predisposed high-density presentation and Th1-type immunity, and whether high ligand density B cells primed Th1 effectors in an MHC genotype that normally presents a low density and the Th2 phenotype. While low ligand density had the capacity to switch phenotype in the Th1 responder, high-density presentation did not alter genetically determined Th2 responder status.
Center for Basic Cancer Research, Kansas State University, Manhattan 66506, USA.
T
T
Schountz
J P
JP
Kasselman
F A
FA
Martinson
L
L
Brown
J S
JS
Murray
D000818:Animals; D017951:Antigen Presentation; D015703:Antigens, CD / Q000276:immunology; D051940:B7-2 Antigen; D002454:Cell Differentiation; D004306:Dose-Response Relationship, Immunologic; D005347:Fibroblasts / Q000378:metabolism; D005838:Genotype; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology; D007156:Immunologic Memory; D008024:Ligands; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex / Q000235:genetics*; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008805:Mice, Inbred A; D010446:Peptide Fragments / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014162:Transfection
D015703:Antigens, CD; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D006183:H-2 Antigens; D000949:Histocompatibility Antigens Class II; D008024:Ligands; D008562:Membrane Glycoproteins; D010446:Peptide Fragments