| First Author | Gilfillan S | Year | 1998 |
| Journal | J Immunol | Volume | 161 |
| Issue | 12 | Pages | 6629-37 |
| PubMed ID | 9862691 | Mgi Jnum | J:130384 |
| Mgi Id | MGI:3771542 | Doi | 10.4049/jimmunol.161.12.6629 |
| Citation | Gilfillan S, et al. (1998) Selection and function of CD4+ T lymphocytes in transgenic mice expressing mutant MHC class II molecules deficient in their interaction with CD4. J Immunol 161(12):6629-37 |
| abstractText | Interactions of the T cell coreceptors, CD4 and CD8, with MHC molecules participate in regulating thymocyte development and T lymphocyte activation and differentiation to memory T cells. However, the exact roles of these interactions in normal T cell development and function remain unclear. CD4 interacts with class II MHC7 molecules via several noncontiguous regions in both the class II MHC alpha- and beta-chains. We have introduced a double mutation that disrupts interaction with CD4 into the I-A(beta)k gene and used this construct to generate transgenic mice expressing only mutant class II MHC. Although CD4+ thymocytes matured to the single-positive stage in these mice, their frequency was reduced by threefold compared with that of wild-type transgenics. Positive selection of CD4+ T cells in the mutant transgenic mice may have been mediated by TCRs with a higher than usual affinity for class II MHC/Ag complexes. In A(beta)k mutant transgenics, peripheral CD4+ lymphocytes promoted B cell differentiation to plasma cells. These CD4+ T cells also secreted IFN-gamma in response to various stimuli (e.g., protein Ag, bacterial superantigen, and alloantigen), but were deficient in IL-2 secretion. Interactions between CD4 and class II MHC molecules appeared to regulate lymphokine production, with a strong bias toward IFN-gamma and against IL-2 in the absence of these interactions. Our results have implications for the manipulation of T cell-dependent immune responses. |
