MHC Class I Allele Dosage Alters CD8 Expression by Intestinal Intraepithelial Lymphocytes

Abstract

The development of TCR αβ+, CD8αβ+ intestinal intraepithelial lymphocytes (IEL) is dependent on MHC class I molecules expressed in the thymus, while some CD8αα+ IEL may arise independently of MHC class I. We examined the influence of MHC I allele dosage on the development CD8+ T cells in RAG 2−/− mice expressing the H-2Db-restricted transgenic TCR specific for the male, Smcy-derived H-Y Ag (H-Y TCR). IEL in male mice heterozygous for the restricting (H-2Db) and nonrestricting (H-2Dd) MHC class I alleles (MHC F1) were composed of a mixture of CD8αβ+ and CD8αα+ T cells, while T cells in the spleen were mostly CD8αβ+. This was unlike IEL in male mice homozygous for H-2Db, which had predominantly CD8αα+ IEL and few mostly CD8− T cells in the spleen. Our results demonstrate that deletion of CD8αβ+ cells in H-Y TCR male mice is dependent on two copies of H-2Db, whereas the generation of CD8αα+ IEL requires only one copy. The existence of CD8αβ+ and CD8αα+ IEL in MHC F1 mice suggests that their generation is not mutually exclusive in cells with identical TCR. Furthermore, our data imply that the level of the restricting MHC class I allele determines a threshold for conventional CD8αβ+ T cell selection in the thymus of H-Y TCR-transgenic mice, whereas the development of CD8αα+ IEL is dependent on, but less sensitive to, this MHC class I allele.