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

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