| First Author | Kim HJ | Year | 2005 |
| Journal | Proc Natl Acad Sci U S A | Volume | 102 |
| Issue | 20 | Pages | 7263-7 |
| PubMed ID | 15883386 | Mgi Jnum | J:99235 |
| Mgi Id | MGI:3581505 | Doi | 10.1073/pnas.0502751102 |
| Citation | Kim HJ, et al. (2005) Coevolution of TCR-MHC interactions: conserved MHC tertiary structure is not sufficient for interactions with the TCR. Proc Natl Acad Sci U S A 102(20):7263-7 |
| abstractText | The specificity for self-MHC that is necessary for T cell function is a consequence of intrathymic selection during which T cell antigen receptors (TCRs) expressed by immature thymocytes are tested for their affinity for self-peptide:self-MHC. The germ-line-encoded segments of the TCR, however, are believed to have an innate specificity for structural features of MHC molecules. We directly tested this hypothesis by generating a transgenic mouse system in which the protein HLA-DM is expressed at the surface of thymic cortical epithelial cells in the absence of classical MHC molecules. The specialized intracellular function of HLA-DM has removed this MHC class II-like protein from the evolutionary forces that have been hypothesized to shape TCR-MHC interactions. Our study shows that a structural mimic of MHC class II is not sufficient to appropriately interact with the TCRs expressed by developing thymocytes. This result emphasizes the unique complementarity of TCR-MHC interactions that are maintained by the evolutionary pressures dictated by positive selection. |
