Abstract:
T-cell antigen receptor (TCR) membrane-negative T-cell mutants can be divided into two groups: 1) those which lack one of the six TCR polypeptides and 2) those which contain a mutated TCR chain. The present experiments reveal a new mechanism for the development of TCR membrane-negative T-cell variants: mutations in splicing consensus motifs causing excision or misreading of an entire exon (exon 3 of the TCRAC or TCRBC genes). C27.15 cells transcribe a TCR alpha chain consisting of TCRAVJCexon1Cexon2-encoded amino acids plus six new amino acids. The assembly defect seems to be that the truncated alpha chain does not interact with CD3 delta molecules; consequently, no TCR alphabeta/CD3 deltaepsilongammaepsilon complexes are formed. E6.E12 cells transcribe a TCR beta chain composed of TCRBVDJCexon1Cexon2-encoded amino acids plus twenty-seven new amino acids, which seem not to form a transmembrane region. The truncated beta chain does associate with CD3 gammaepsilon heterodimers, yet no TCR alphabeta/CD3 deltaepsilongammaepsilon complexes are made. This may be due either to low assembly of TCR beta/CD3 gammaepsilon trimers or to lack of access of the mutated TCR beta/CD3 gammaepsilon trimers to the TCR alpha/CD3 deltaepsilon compartment in the endoplasmic reticulum.