THE SHORT EXTRACELLULAR DOMAIN OF THE T-CELL RECEPTOR ZETA-CHAIN IS INVOLVED IN ASSEMBLY AND SIGNAL-TRANSDUCTION

The zeta chain is required in the TCR complex to guarantee its surface expression and function. However, an understanding of the interaction (s) between the zeta chain and the other proteins in the TCR/CD3 has n ot yet been achieved. In this report, we attempt to assign a functiona l role to the short extracellular (EC) domain of the zeta chain by stu dying its unique positive charge, a lysine at position 9, because of i ts interesting location to the interchain disulphide bond of the zeta chain homodimer. We show that amino acid exchanges of lysine 9 to glyc ine, serine, cysteine or asparagine generate TCR complexes which are c learly defective in antigenic signalling. Interestingly, the non-conse rvative point mutations were segregating TCR complex signalling pathwa ys. However, lysine 9 is not critical for TCR complex surface expressi on unless the positively charged lysine is exchanged for the negativel y charged amino acid aspartic acid. The zeta chain mutant bearing a ly sine to cysteine exchange is the sole mutant to be inefficiently co-pr ecipitated with the TCR/CD3 complex suggesting a loose interaction of the zeta chain within the TCR complex. (C) 1998 Elsevier Science Ltd. All rights reserved.