2F53

Directed Evolution of Human T-cell Receptor CDR2 residues by phage display dramatically enhances affinity for cognate peptide-MHC without apparent cross-reactivity

2F53 の概要

• エントリーDOI: 10.2210/pdb2f53/pdb
• 関連するPDBエントリー: 2F54
• 分子名称: HLA class I histocompatibility antigen, Beta-2-microglobulin, Cancer/testis antigen 1B, ... (8 entities in total)
• 機能のキーワード: t-cell receptor, cdr2, phage display, mutant, high affinity, ny-eso-1, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Membrane; Single-pass type I membrane protein: P01892; Secreted: P61769; Cytoplasm: P78358
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 93672.14

構造登録者

Rizkallah, P.J.,Jakobsen, B.K.,Dunn, S.M.,Sami, M. (登録日: 2005-11-25, 公開日: 2006-04-25, 最終更新日: 2024-11-20)

主引用文献

Dunn, S.M.,Rizkallah, P.J.,Baston, E.,Mahon, T.,Cameron, B.,Moysey, R.,Gao, F.,Sami, M.,Boulter, J.,Li, Y.,Jakobsen, B.K.
Directed evolution of human T cell receptor CDR2 residues by phage display dramatically enhances affinity for cognate peptide-MHC without increasing apparent cross-reactivity.
Protein Sci., 15:710-721, 2006

PubMed Abstract: The mammalian alpha/beta T cell receptor (TCR) repertoire plays a pivotal role in adaptive immunity by recognizing short, processed, peptide antigens bound in the context of a highly diverse family of cell-surface major histocompatibility complexes (pMHCs). Despite the extensive TCR-MHC interaction surface, peptide-independent cross-reactivity of native TCRs is generally avoided through cell-mediated selection of molecules with low inherent affinity for MHC. Here we show that, contrary to expectations, the germ line-encoded complementarity determining regions (CDRs) of human TCRs, namely the CDR2s, which appear to contact only the MHC surface and not the bound peptide, can be engineered to yield soluble low nanomolar affinity ligands that retain a surprisingly high degree of specificity for the cognate pMHC target. Structural investigation of one such CDR2 mutant implicates shape complementarity of the mutant CDR2 contact interfaces as being a key determinant of the increased affinity. Our results suggest that manipulation of germ line CDR2 loops may provide a useful route to the production of high-affinity TCRs with therapeutic and diagnostic potential.

PubMed: 16600963
DOI: 10.1110/ps.051936406

実験手法

X-RAY DIFFRACTION (2.1 Å)