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MHC Class I Allele Dosage Alters CD8 Expression by Intestinal Intraepithelial Lymphocytes¹

Bradley S. Podd^2,*, Caroline Åberg^2,*, Kimberly L. Kudla^*, Lataya Keene^*, Erin Tobias^* and Victoria Camerini^3,*,

^* Department of Pediatrics and Beirne B. Carter Center for Immunology, University of Virginia Health Sciences Center, Charlottesville, VA 22908

The development of TCR ⁺, CD8⁺ intestinal intraepithelial lymphocytes (IEL) is dependent on MHC class I molecules expressed in the thymus, while some CD8⁺ 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-2D^b-restricted transgenic TCR specific for the male, Smcy-derived H-Y Ag (H-Y TCR). IEL in male mice heterozygous for the restricting (H-2D^b) and nonrestricting (H-2D^d) MHC class I alleles (MHC F₁) were composed of a mixture of CD8⁺ and CD8⁺ T cells, while T cells in the spleen were mostly CD8⁺. This was unlike IEL in male mice homozygous for H-2D^b, which had predominantly CD8⁺ IEL and few mostly CD8^- T cells in the spleen. Our results demonstrate that deletion of CD8⁺ cells in H-Y TCR male mice is dependent on two copies of H-2D^b, whereas the generation of CD8⁺ IEL requires only one copy. The existence of CD8⁺ and CD8⁺ 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 CD8⁺ T cell selection in the thymus of H-Y TCR-transgenic mice, whereas the development of CD8⁺ IEL is dependent on, but less sensitive to, this MHC class I allele.

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