Class II-restricted T cell receptor engineered in vitro for higher affinity retains peptide specificity and function.

ABSTRACT: The T cell receptor (TCR) alphabeta heterodimer determines the peptide and MHC specificity of a T cell. It has been proposed that in vivo selection processes maintain low TCR affinities because T cells with higher-affinity TCRs would (i) have reduced functional capacity or (ii) cross-react with self-peptides resulting in clonal deletion. We used the class II-restricted T cell clone 3.L2, specific for murine hemoglobin (Hb/I-E(k)), to explore these possibilities by engineering higher-affinity TCR mutants. A 3.L2 single-chain TCR (Vbeta-linker-Valpha) was mutagenized and selected for thermal stability and surface expression in a yeast display system. Stabilized mutants were used to generate a library with CDR3 mutations that were selected with Hb/I-E(k) to isolate a panel of affinity mutants

SUBMITTER: Weber KS 

PROVIDER: S-EPMC1323173 | biostudies-literature | 2005 Dec

REPOSITORIES: biostudies-literature