Investigations of the major histocompatibility complex of the rabbit (RLA) have led to identification of a nonpolymorphic gene encoding the class II DO beta chain. RLA-DOB is nearly identical to its human counterpart and has large differences from other class II beta chains. The product is expressed only on mature B cells and to a limited extent in thymus. In order to study the the function of the DOB product, monoclonal and polyclonal antibodies against human and rabbit DOB are in preparation. The antibodies will be used to localize DOB and to isolate the DOB complex (putatively DN/DO) and eventually to ascertain whether a peptide or other molecule is associated with the molecular complex. Efforts to construct a complete physical map of the rabbit MHC are in progress and attempts to order the various MHC regions in the rabbit continue. Previous results showed that class II and class I regions were adjacent with no interposition of Class III genes. Studies of class III gene prompted a study of heat shock protein 70 which is expressed on HTLV-I infected cells. Anti-heat shock protein (HSP) antibodies were observed in the sera of rabbits after inoculation with the HTLV-I cell lines. One cell line RH/K34, which failed to raise a response to HSP70, was shown subsequently to cause lethal leukemia when live cells were injected into unrelated outbred rabbits. Injection of sublethal doses of this line failed to elicit anti HSP although injection of cell free virus from the line did so. Rabbits with detectable levels of anti HSP70 antibodies prior to challenge with lethal doses of live RH/K34 cells were resistant to its lethal effects suggesting that HSP immunity (which is autoimmunity) may influence the outcome of RH/K34 pathogenicity and may have general implications to viral immunity. In order to study the interaction between HSP and HTLV-1 infection, specific polyclonal and monoclonal antibodies against HSP 70 and HSP 90 will be tested to determine whether disease and/ or infection can be inhibited by passive or active immunization.
