Role of transmembrane domains in the functions of B- and T-cell receptors.

The antigen receptors on the surface of B- and T-lymphocytes are complexes of several integral membrane proteins, essential for their proper expression and function. Recent studies demonstrated that transmembrane (TM) domains of the components of these receptors play a critical role in their association and function. It was specifically demonstrated that in many cases point mutations in the TM domains can partially or completely disrupt the receptor surface expression and function. Here we review studies of the TM domains of B- and T-cell receptors. Furthermore, we use a novel method, PHDtopology, to provide estimates of the exact locations and lengths of the TM domains of the subunit components of these receptors. Most previous studies used single residue hydrophobicity as a criterion for determining the position and length of the TM domains. In contrast, PHDtopology utilizes a system of neural networks and the evolutionary information contained in multiple alignments of related sequences to predict the location, length, and orientation of transmembrane helices. Present results significantly differ from most published estimates of the TM domains of the B- and T-cell receptor components, primarily in the length of the TM domains. These results may lead to modification of putative TM motifs and re-interpretation of the results of studies using mutated TM domains. The availability of PHDtopology on the Internet would make it a valuable tool in the future studies of the TM domains of integral membrane proteins.