Analysis of intraepithelial lymphocytes from major histocompatibility complex (MHC)-deficient mice: No evidence for a role of MHC class II antigens in the positive selection of Vδ4+γδ T cells

Three-color flow cytometric analysis was carried out with intraepithelial lymphocytes from mice deficient in expression of major histocompatibility complex (MHC) antigens. These experiments were done to address the possible role of MHC class II molecules in the positive selection of Vδ4⁺ γδ T cells. By analyzing mice deficient MHC class II antigens alone or in combination with MHC class I antigens, no evidence was found for positive selection of Vδ4⁺ cells among CD8a⁺ or CD4^?CD8^? subpopulations of γδ T cell receptor-positive cells. Because V54⁺, CD8a⁺ cells were reported to be positively selected on I-E^k and hybrid I-E^k/b molecules, class II-deficient animals were crossed with I-E^k transgenic mice and progeny examined for Vδ4 expression. Again, no evidence for positive selection was found. Interestingly, in MHC class I-deficient animals, the total number of γδ T cells was about twofold higher than in control and MHC class II-deficient mice and the proportion of V8δ-expressing cells was correspondingly decreased. Taken together, these results cast doubt on a major role for conventional MHC antigens in shaping the γδ T cell repertoire of intraepithelial lymphocytes.