V(D)J germline gene repertoire analysis of monoclonal D antibodies and theimplications for D epitope specificity

Citation
Ws. Perera et al., V(D)J germline gene repertoire analysis of monoclonal D antibodies and theimplications for D epitope specificity, TRANSFUSION, 40(7), 2000, pp. 846-855
Citations number
55
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Hematology,"Cardiovascular & Hematology Research
Journal title
TRANSFUSION
ISSN journal
0041-1132 → ACNP
Volume
40
Issue
7
Year of publication
2000
Pages
846 - 855
Database
ISI
SICI code
0041-1132(200007)40:7<846:VGGRAO>2.0.ZU;2-D
Abstract
BACKGROUND: The D antigen is a highly immunogenic human RBC antigen. Alloim munization against the D antigen produces high-affinity antibodies that cau se hemolytic transfusion reactions and HDN. STUDY DESIGN AND METHODS: Cloning and subsequent sequence analysis of 11 ne w samples of monoclonal anti-D was performed in an attempt to identify V(D) J germline gene usage. Sequences were compared and analyzed with 37 previou sly published samples of anti-D for identification of V-H acid V-L pairings , canonical structures, and conformation of restricted germline gene usage. RESULTS: The V-H and V-L pairings used by the new D MoAbs resulted in seven canonical combinations, three of which had not been described previously. Preferential usage of gene segments from the VH3 and VH4 families and of D3 , D6, JH6, and DPK9 germline gene segments was also determined. Three sampl es of anti-D from different donors were found to use similar V-H and V-kapp a germline genes, despite the fact that two of the antibodies recognized ep D6/7 and the third recognized epD1. From the cumulative analysis of the ant i-D IgG, 24 V-H and V-L gene pairings were identified, resulting in only 10 canonical structures. CONCLUSIONS: Despite the potential for diversity, only a minority of V-H an d V-L germline genes are used by anti-D. Consequently, V-H and V-L pairings and the resulting canonical structures are similarly restricted.