title: Influence of antigen density on degree of clonal deletion in T cell receptor transgenic mice.
abstract: The extent of peripheral clonal deletion of the T cell antigen receptor (TCR) from a CD8-dependent cytotoxic T lymphocyte of H-2k origin with alloreactivity for H-2Kb was measured in a TCR transgenic (Tg) model by use of a clonotype-specific mAb (anti-Ti mAb). Deletion varied depending on whether the TCR Tg was expressed in mice heterozygous (H-2k x b) or homozygous (H-2b x b) for the H-2Kb antigen. CD8 surface staining and functional analyses of peripheral T cells stimulated with polyclonal activators in bulk culture or by limiting dilution confirmed that in the H-2b x b mice few Ti+ cells were generated as measured by anti-Ti mAb-dependent target cell killing; while such cells could readily be detected in the H-2k x b mice. The latter maintained non-responsiveness to H-2Kb, as measured by cytolysis of H-2Kb-expressing tumor target cells, due to their down-regulation of surface CD8 expression. The question of whether the difference between H-2b x b and H-2k x b mice was due to the influence of positive selection imposed by the k haplotype in the H-2k x b hybrid, or to the lower antigen density in heterozygous than homozygous mice was addressed by analysis of H-2b x d Tg mice, H-2d being a non-selecting haplotype. Results obtained were similar for H-2b x d and H-2k x b Tg mice, suggesting that the density of the H-2Kb antigen may be one of the parameters controlling the extent of clonal deletion in the thymus.
authors.affiliation: Centre d'Immunologie INSERM-CNRS de Marseille-Luminy, France.
authors.forename: N
authors.initials: N
authors.lastname: Auphan
authors.forename: G
authors.initials: G
authors.lastname: Schönrich
authors.forename: M
authors.initials: M
authors.lastname: Malissen
authors.forename: M
authors.initials: M
authors.lastname: Barad
authors.forename: G
authors.initials: G
authors.lastname: Hämmerling
authors.forename: B
authors.initials: B
authors.lastname: Arnold
authors.forename: B
authors.initials: B
authors.lastname: Malissen
authors.forename: A M
authors.initials: AM
authors.lastname: Schmitt-Verhulst
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D006183:H-2 Antigens / Q000235:genetics / Q000378:metabolism*; D007108:Immune Tolerance; D051379:Mice; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology
chemical_list: D015704:CD4 Antigens; D016827:CD8 Antigens; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D016693:Receptors, Antigen, T-Cell, alpha-beta