Differential thymic selection outcomes stimulated by focal structural alteration in peptide/major histocompatibility complex ligands
AUTOR(ES)
Ghendler, Yoseph
FONTE
The National Academy of Sciences
RESUMO
The T lineage repertoire is shaped by T cell receptor (TCR)-dependent positive and negative thymic selection processes. Using TCR-transgenic (N15tg) β2-microglobulin-deficient (β2m−/−) RAG-2−/− H-2b 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 Å 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 Vα repertoire contributes in a significant way to positive selection.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=21461Documentos Relacionados
- Shared fine specificity between T-cell receptors and an antibody recognizing a peptide/major histocompatibility class I complex.
- Expression of endogenous peptide-major histocompatibility complex class II complexes derived from invariant chain-antigen fusion proteins.
- Production, specificity, and functionality of monoclonal antibodies to specific peptide–major histocompatibility complex class II complexes formed by processing of exogenous protein
- The role of peptides in thymic positive selection of class II major histocompatibility complex-restricted T cells
- Minimum structural requirements for peptide presentation by major histocompatibility complex class II molecules: implications in induction of autoimmunity.