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 expressio n and function. Recent studies demonstrated that transmembrane (TM) domains of the components of these receptors play a critical role in their associa tion and function. It was specifically demonstrated that in many cases poin t mutations in the TM domains can partially or completely disrupt the recep tor surface expression and function. Here we review studies of the TM domai ns of B- and T-cell receptors. Furthermore. we use a novel method, PHDtopol ogy, to provide estimates of the exact locations and lengths of the TM doma ins of the subunit components of these receptors. Most previous studies use d single residue hydrophobicity as a criterion for determining the position and length of the TM domains. In contrast, PHDtopology utilizes a system o f neural networks and the evolutionary information contained in multiple al ignments of related sequences to predict the location, length, and orientat ion of transmembrane helices. Present results significantly differ from mos t published estimates of the TM domains of the B- and T-cell receptor compo nents, 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 I nternet would make it a valuable tool in the future studies of the TM domai ns of integral membrane proteins. (C) 1998 Elsevier Science B.V. All rights reserved.