| First Author | Ghendler Y | Year | 1998 |
| Journal | Proc Natl Acad Sci U S A | Volume | 95 |
| Issue | 17 | Pages | 10061-6 |
| PubMed ID | 9707600 | Mgi Jnum | J:119802 |
| Mgi Id | MGI:3703284 | Doi | 10.1073/pnas.95.17.10061 |
| Citation | Ghendler Y, et al. (1998) Differential thymic selection outcomes stimulated by focal structural alteration in peptide/major histocompatibility complex ligands. Proc Natl Acad Sci U S A 95(17):10061-6 |
| abstractText | The T lineage repertoire is shaped by T cell receptor (TCR)-dependent positive and negative thymic selection processes. Using TCR-transgenic (N15tg) beta2-microglobulin-deficient (beta2m-/-) RAG-2(-/-) H-2(b) mice specific for the VSV8 (RGYVYQGL) octapeptide bound to Kb, we identified a single weak agonist peptide variant V4L (L4) inducing phenotypic and functional T cell maturation. The cognate VSV8 peptide, in contrast, triggers negative selection. The crystal structure of L4/Kb was determined and refined to 2.1 A for comparison with the VSV8/Kb structure at similar resolution. Aside from changes on the p4 side chain of L4 and the resulting alteration of the exposed Kb Lys-66 side chain, these two structures are essentially identical. Hence, a given TCR recognizes subtle distinctions between highly related ligands, resulting in dramatically different selection outcomes. Based on these finding and the recent structural elucidation of the N15-VSV8/Kb complex, moreover, it appears that the germ-line Valpha repertoire contributes in a significant way to positive selection. |
