TAP-independent selection of CD8(+) intestinal intraepithelial lymphocytes

Intestinal intraepithelial lymphocytes (IEL) are mostly CD8 single positive T cells, IEL with a TCR-alpha beta that are CD8 single positive are absent from beta(2)-microglobulin (beta(2)m)-deficient mice, consistent with the idea that these IEL, like other TCR-alpha beta(+),CD8(+) T cells, require class I molecules for positive selection, In contrast, here we show that substantial numbers of TCR-alpha beta(+),CD8 single positive IEL are present in mice deficient for the transporter associated with Ag processing 1 (TAP I) gene, although T cells with this phenotype are absent from thymus, spleen, and lymph nodes of these same mice. The majority of TCR-alpha beta(+),CD8 single positive IEL in TAP-deficient mice expresses CD8 molecules composed of alpha alpha homodimers and they express a diverse set of VP gene segments. In addition, the number of TCR-alpha beta(+),CD4/CD8 double positive IEL is decreased in beta(2)m-deficient mice but not in TAP-deficient mice, The dependence of the two TCR-alpha beta(+) IEL populations that express CD8 alpha alpha homodimers on beta(2)m as opposed to TAP molecules is striking. It suggests that TAP-independent but beta(2)m-requiring nonclassical class I molecules expressed by cells in the intestine, such as the thymus leukemia Ag and CD1, could play a pivotal role in the development and/or the accumulation of major subpopulations of TCR-alpha beta(+) IEL.