The intracellular fate of T cell antigen receptor (TCR) subunits (apr&) is determined by their assembly in the endoplasmic reticulum (ER). To study the structural bases for this tight correlation between assembly and intracellular fate, we sought to define the nature of determinants for both ER degradation and subunit assembly within the TCR-a chain. We found that a 9 amino acid transmembrane sequence of the TCR-a chain, containing 2 critical charged resldues, was sufficient to cause ER degradation when placed in the context of the Tat antigen, used here as a reporter protein. CD34 assembled with chimeric proteins containing this short transmembrane sequence, and this assembly resulted In abrogation of targeting for ER degradation. Thus, the colocalizatlon of determinants for ER degradation and sites of subunit interactions explains how the fate of some newly synthesized TCR chains can be decided on the basis of their assembly status.