| First Author | Sakihama T | Year | 2000 |
| Journal | Eur J Immunol | Volume | 30 |
| Issue | 1 | Pages | 279-90 |
| PubMed ID | 10602051 | Mgi Jnum | J:289865 |
| Mgi Id | MGI:6432522 | Doi | 10.1002/1521-4141(200001)30:1<279::AID-IMMU279>3.0.CO;2-5 |
| Citation | Sakihama T, et al. (2000) Human CD4 residue Phe 43 is critical for repertoire development and maturation of MHC class II restricted CD4 single-positive T lineage cells in vivo. Eur J Immunol 30(1):279-90 |
| abstractText | To determine the functional significance of structural alteration of CD4-MHC class II interaction in vivo, two human (h)CD4-transgenic (tg) mice were established on a murine (m)CD4(-/-) H-2(b) background. The MHC class II binding-competent hCD4 (R240AhCD4) rescues the number and helper activity of hCD4(+)CD8(-) single-positive (SP) mature T cells in mCD4(-/-) mice. In contrast, the MHC class II binding-deficient F43I hCD4 mutant cannot facilitate normal differentiation of double-positive thymocytes to CD4(+)CD8(-) SP thymocytes. Hence, only 20 - 25% of CD4(+)CD8(-) SP T cells found in wild-type or R240A hCD4tg mice are generated, with resultant diminished helper responses. Differentiation of F43I hCD4 SP T cells is MHC class II but not class I dependent as demonstrated by crossing F43I hCD4tg mice onto MHC-deficient mice. These cells show a different pattern of TCR Valpha and Vbeta gene usage relative to comparable R240A hCD4 SP T cells from R240 AhCD4tg animals. Expression of activation markers including CD25 and CD69 on F43I hCD4 SP T cells suggests that autoreactive specificites may not have been eliminated intrathymically. Collectively, the results show that CD4-MHC class II interaction significantly influences intrathymic repertoire selection. |
