Quantitation of the cell surface level of Ld resulting in positive versus negative selection of the 2C transgenic T cell receptor in vivo.
The 2C transgenic TCR is positively selected on Kb and is alloreactive for and negatively selected on Ld. To test an avidity model for positive selection, mice were bred to express different levels of surface Ld by varying the number of gene copies encoding beta 2-microglobulin (beta 2m) or Ld heavy chain. Whereas mice expressing 35% Ld (beta 2m+/- Ld+/-) negatively selected the 2C TCR, mice expressing 2% Ld (beta 2m-/- Ld+/-) positively selected the 2C TCR. Furthermore, 2C cytotoxic T lymphocytes selected on 2% Ld showed peptide-specific cytolytic activity against Ld/p2Ca targets. These findings provide clear in vivo evidence that positive selection can occur on very low levels of the same class I antigen capable of negative selection when expressed at higher levels.
Cook
J R
JR
Department of Genetics, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Wormstall
E M
EM
Hornell
T
T
Russell
J
J
Connolly
J M
JM
Hansen
T H
TH
D000818:Animals; D000954:Antigens, Surface / Q000235:genetics; D015704:CD4 Antigens / Q000235:genetics; D016827:CD8 Antigens / Q000235:genetics; D018628:Gene Dosage; D006183:H-2 Antigens / Q000235:genetics*; D064532:Histocompatibility Antigen H-2D; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D016130:Immunophenotyping; D007519:Isoantigens / Q000235:genetics; D018655:Lymphocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D013154:Spleen; D019076:Transgenes / Q000276:immunology*; D001613:beta 2-Microglobulin / Q000235:genetics
D000954:Antigens, Surface; D015704:CD4 Antigens; D016827:CD8 Antigens; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D015395:Histocompatibility Antigens Class I; D007519:Isoantigens; D011948:Receptors, Antigen, T-Cell; D001613:beta 2-Microglobulin