Positive selection of an MHC class-I restricted TCR in the absence of classical MHC class I molecules

The H-2L(d) alloreactive 2C T cell receptor (TCR) is commonly considered as being positively selected on the H-2K(b) molecule. Surprisingly, 2C TCR(+) CD8(+) single-positive T cells emerge in massive numbers in fetal thymic organ culture originating from 2C transgenic, H-2K(b)D(b−/−) (2C(+)K(b)D(b−/−)) but not in fetal thymic organ culture from β(2)-microglobulin(−/−) 2C transgenic animals. Mature CD8(+) T cells are observed in newborn but not in adult 2C(+)K(b)D(b−/−) mice. These CD8(+) T cells express the α(4)β(7) integrin, which allows them to populate the intestine, a pattern of migration visualized by intrathymic injection of FITC and subsequent accrual of FITC-labeled lymphocytes in the gut. We conclude that the 2C TCR is reactive not only with H-2L(d) and H-2K(b), but also with nonclassical MHC class I products to enable positive selection of 2C(+) T cells in the fetal and newborn thymus and to support their maintenance in the intestine.