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+ C D8+ 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 beta2-microglobulin(-/-) 2C tran sgenic animals. Mature CD8+ T cells are observed in newborn but not in adul t 2C(+)K(b)D(b-/-)mice. These CD8(+) T cells express the alpha (4)beta (7) integrin, which allows them to populate the intestine, a pattern of migrati on visualized by intrathymic injection of FITC and subsequent accrual of FI TC-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 p roducts to enable positive selection of 2C(+) T cells in the fetal and newb orn thymus and to support their maintenance in the intestine.