THE PRIMARY STRUCTURE OF THE FAB FRAGMENT OF PROTEIN KAU, A MONOCLONAL IMMUNOGLOBULIN-M COLD AGGLUTININ

The complete amino acid sequence of the Fab fragment of protein KAU, a human monoclonal cold agglutinin (IgM(k)) with anti-I activity, was determined. The light chain (L-chain) consists of 215 residues; the variable (V)L region belongs to the Hum/Kv325/K(IIIb) sub-subgroup that is preferentially selected in human IgM autoimmune response. The joining (J) region is encoded by the J(k4) gene, and the constant region (C)L domain expresses the km3 allotypic marker. The Fd fragment contains 232 amino acids, and 120 of them comprise the variable domain. The V(H) region corresponds to the V(H)IV subgroup and is closely related to the V(H)IV 2.1 gene isolated from genomic DNA expressed in peripheral blood of a healthy Caucasian. The complementary-determining region 1 has a unique amino acid (Asp) at position 31, and the complementary-determining region 3 codified by the diversity segment (D) gene, shows poor homology with other known D sequences. The joining segment with two unusual substitutions at the D-J junction is encoded by the J(H4) gene. Thus, cold agglutinin KAU is an IgM, V(kIIb)-J(k4)-Km3; V(H)IV-J(H4)-C-mu.