THE CYTOPLASMIC AND TRANSMEMBRANE DOMAINS OF MHC CLASS-II BETA-CHAINS DELIVER DISTINCT SIGNALS REQUIRED FOR MHC CLASS II-MEDIATED B-CELL ACTIVATION

Class II-mediated signals play potential roles in B cell activation and antigen presentation. The regions of the class II molecule participating in B cell signaling are incompletely defined. Our prior analysis of structural requirements of the cytoplasmic domain of A(beta) revealed that only the eight membrane-proximal residues are required for signaling. Here, we report that the sequence and position of two of these are critical, and present direct evidence that the A(beta) transmembrane domain is also involved in signaling, via a pathway distinct from the cytoplasmic domain. These results demonstrate that specific regions in both the cytoplasmic and transmembrane domains of the class II molecule have distinct signaling functions.