Anti-D and anti-i activities are inseparable in V4-34-encoded monoclonal anti-D: the same framework 1 residues are required for both reactivities

作者：Thorpe Susan J^*; Ball Christine; Fox Bernard; Thompson Keith M; Thorpe Robin; Bristow Adrian

来源：Transfusion, 2008, 48(5): 930-940.

DOI：10.1111/j.1537-2995.2007.01624.x

Background: The heavy-chain V4-34 germline gene segment is mandatory for pathologic cold-reacting autoantibodies with anti-I/i specificity (cold agglutinins) and is also preferentially used by monoclonal immunoglobulin M alloantibodies against D and other Rh antigens. The use of the V4-34 segment by monoclonal anti-D has previously been shown to also confer anti-I/i reactivity (cold agglutinin activity), which has implications for the use of such antibodies for Rh blood typing. V4-34 framework 1 (FR1) sequence is believed to be critical for cold agglutinin activity of cold agglutinins.
Study design and methods: The aim of this investigation was to use site-directed mutagenesis of a recombinant V4-34-encoded anti-D to determine the contribution of V4-34 FR1 sequence to anti-D activity and whether mutational modifications in the FR1 region could separately alter anti-D and anti-i activities.
Results: The results show that amino acid changes in V4-34 FR1 at W7, A23, and Y25 have a profound effect on anti-D activity as well as on anti-i activity. It was not possible to substantially reduce or remove anti-i activity without reducing anti-D activity to a comparable extent.
Conclusions: The same nonpolar hydrophobic amino acids in FR1 are critical for maintaining both anti-D and anti-i activity. It is proposed that these residues influence the conformation of the antigen-binding site.

• 出版日期2008-5
• 单位中国食品药品检定研究院