TCR BINDING DIFFERS FOR A BACTERIAL SUPERANTIGEN (SEE) AND A VIRAL SUPERANTIGEN (MTV-9)

Both superantigens (SAG) and many anti-TCR monoclonal antibodies (mAb) have specificity for the V beta region of the TCR encoded by TCRBV ge nes. For instance the bacterial SAG staphylococcal enterotoxin E (SEE) the retroviral SAG MTV-9 and the mAb OT145 each react with human T ce lls expressing BV6S7. This BV gene encodes two common alleles, We foun d that SEE and the mAb preferentially activate T cells expressing BV6S 71 as opposed to BV6S7*2, but Mtv-9 activates T cells expressing eith er allele. Thus binding to the TCR differs between the two SAGs. A mut ation in the TCR HVR-4 region of BVbS71 (G72E), where the two BV6S7 a lleles differ, indicated that HVR-4 is a component of the binding site for SEE and for the mAb OT145. BV6S72 has a charged E72 which may re sult in electrostatic repulsion of SEE, as SEE contains a similarly ac idic aspartic acid residue at a TCR interaction site (204D).