Qa-2-dependent selection of CD8α/α T cell receptor α/β+ cells in murine intestinal intraepithelial lymphocytes

Murine intestinal intraepithelial lymphocytes (iIELs) are made up of a heterogeneous mix of T cells with unique phenotypes. Whereas CD8(+) T cells in peripheral lymphoid organs use CD8 alpha/beta and are selected on MHC class Ia molecules, a majority of iIELs use CD8 alpha/alpha. Here, we report that the presence of CD8 alpha/alpha TCR-alpha/beta cells in iIELs is independent of classical MHC class I molecules K-b and D-b, as illustrated by their presence in K-b/D-b double-knockout mice and in mice lacking a nonclassical MHC class I molecule, CD1d. Most strikingly, their presence is decreased by similar to 70% in mice lacking transporter associated with antigen processing (TAP). The TAP-dependent nonclassical MHC class I molecule Qa-2 is strongly implicated in the presence of these cells, as inferred from the low numbers of CD8 alpha/alpha TCR-alpha/beta T cells in mice deficient in Qa-2 genes. Second, a Qa-2-transgenic mouse made in a Qa-2(-) strain showed an increase in the numbers of CD8 alpha/alpha cells among its iIELs. Thus, the presence of CD8 alpha/alpha TCR-alpha/beta cells in iIELs is mainly dependent on the nonclassical MHC class I molecule Qa-2.