Molecular structure of eight human autoreactive monoclonal antibodies

The heavy (H) and light (L) chain V-region sequences of eight human autorea ctive immunoglobulin M (IgM) monoclonal antibodies (mAbs: BY-4, BY-7, BY-12 , IRM-3. IRM-7, IRM-8, IRM-10 and CDC-1) were determined at the cDNA level. All V-H and V-L families were identified. Four different VH families were represented, V(H)3 being the most common as five of the mAbs (BY-7, BY-12, IRM-3, IRM-8 and CDC-1) used genetic elements of this family, whereas V(H)1 , V(H)2 and V(H)4 were only present in IRM-7, BY-4 and IRM-IO, respectively . BY-4, BY-7, BY-12, IRM-7 and IRM-10 reacted with a variety of self as wel l as non-self antigens, thus exhibiting polyreactive behaviour. Comparison of the gene segments utilized by these mAbs with their germline counterpart s revealed that the gene segments were close to germline configuration. The length of H-CDR3 was found to be relatively long (27-60 nucleotides) among the polyreactive mAbs and the presence of Tyr and Trp residues in this reg ion seems to be of vital importance for polyreactivity. We have analysed th e utilization of gene elements and the presence of amino acid residues in r egions particularly important for antigen binding, such as CDR. Common mole cular features relating to the function of the mAbs are discussed.