Quantitation of the cell surface level of L-d resulting in positive versus negative selection of the 2C transgenic T cell receptor in vivo

The 2C transgenic TCR is positively selected on K-b and is alloreactive for and negatively selected on L-d. To test an avidity model for positive selection, mice were bred to express different levels of surface L-d by varying the number of gene copies encoding beta(2)-microglobulin (beta(2)m) or L-d heavy chain. Whereas mice expressing 35% L-d (beta(2)m(+/-) Ld+/-) negatively selected the 2C TCR, mice expressing 2% L-d (beta(2)m(-/-) Ld+/-) positively selected the 2C TCR. Furthermore, 2C cytotoxic T lymphocytes selected on 2% L-d showed peptide-specific cytolytic activity against L-d/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.