The amino acid sequence of a monoclonal gamma 3-heavy chain from a patientwith articular gamma-heavy chain deposition disease

Abnormal deposition of proteins, including monoclonal immunoglobulin gamma- heavy chains, may cause tissue damage and organ dysfunction. We here report the amino acid sequence of the free gamma-heavy chains present in serum an d urine of the first reported case (patient G. L.) of synovial heavy chain deposition disease. The protein was heavily deleted and consisted of the hi nge, in addition to the CH2 and CH3 domains, in a dimeric form, thus lackin g its variable domain as well as the CH1 domain. The sequence was consisten t with the gamma 3 subclass (gamma 3GL). Gm typing revealed the gamma 3 all otypes G3m(b0) and G3m(b1) in accordance with the residues Pro123, Phe128, Thr171 and Phe268 in gamma 3GL. Furthermore, the gamma 3GL molecule was gly cosylated at Asn in position 129. Finally, the gamma 3GL protein was shown to contain a typical binding site for the first complement component, C1q, namely the residues Glu150, Lys152 and Lys154, with the potential of bindin g and activating complement, causing tissue damage following deposition.