TAP-INDEPENDENT SELECTION OF CD8(+) INTESTINAL INTRAEPITHELIAL LYMPHOCYTES

Intestinal intraepithelial lymphocytes (IEL) are mostly CD8 single pos itive T cells, IEL with a TCR-alpha beta that are CD8 single positive are absent from beta(2)-microglobulin (beta(2)m)-deficient mice, consi stent with the idea that these IEL, like other TCR-alpha beta(+),CD8() T cells, require class I molecules for positive selection, In contra st, here we show that substantial numbers of TCR-alpha beta(+),CD8 sin gle positive IEL are present in mice deficient for the transporter ass ociated with Ag processing 1 (TAP I) gene, although T cells with this phenotype are absent from thymus, spleen, and lymph nodes of these sam e mice. The majority of TCR-alpha beta(+),CD8 single positive IEL in T AP-deficient mice expresses CD8 molecules composed of alpha alpha homo dimers and they express a diverse set of VP gene segments. In addition , the number of TCR-alpha beta(+),CD4/CD8 double positive IEL is decre ased in beta(2)m-deficient mice but not in TAP-deficient mice, The dep endence of the two TCR-alpha beta(+) IEL populations that express CD8 alpha alpha homodimers on beta(2)m as opposed to TAP molecules is stri king. It suggests that TAP-independent but beta(2)m-requiring nonclass ical class I molecules expressed by cells in the intestine, such as th e thymus leukemia Ag and CD1, could play a pivotal role in the develop ment and/or the accumulation of major subpopulations of TCR-alpha beta (+) IEL.