Extensive restrictions in the VH sequence usage of the human antibody response against the Rhesus D antigen. Export

@article{citeulike:1361549, abstract = {Anti-Rhesus D immunoglobulin purified from human sera is used as a prophylactic reagent in Rhesus D negative women at risk of alloimmunization during pregnancy. We are currently developing a Rhesus D antigen-specific recombinant polyclonal antibody drug lead for replacing the existing blood derived-products. By analyzing the RhD-specific antibody VH repertoires from eight alloimmunized women we found, in agreement with previous studies, a strong preference for the VH 3-33 "superspecies" gene segments which encompasses the IGHV3-30-3*01, IGHV3-30*18, and IGHV3-33*01 VH alleles. Even more extensive genetic restriction was observed among five donors, which produced antibodies of identical V-D-J usage and CDR3 loop length and joining regions of similar amino acid composition. In addition, we find a high degree of sequence relatedness to previously isolated anti-Rhesus D antibodies. Such close homology in VH domains indicates that significant structural restrictions are operating in the selection of antibodies recognizing RhD as seen for T cell receptors. Moreover, some VH domains were isolated in their germline configuration indicating that anti-RhD antibodies of relatively high affinity are present in the na\"{i}ve antibody repertoire of Rhesus negative individuals which offers an explanation for the strong and clinically significant immunogenicity of the Rhesus D.}, address = {Symphogen A/S, Elektrovej, Building 375, 2800 Lyngby, Denmark. psa@symphogen.com}, author = {Andersen, P. S. and Haahr-Hansen, M. and Coljee, V. W. and Hinnerfeldt, F. R. and Varming, K. and Bregenholt, S. and Haurum, J. S.}, citeulike-article-id = {1361549}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.molimm.2006.02.021}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/16581131}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=16581131}, doi = {10.1016/j.molimm.2006.02.021}, issn = {0161-5890}, journal = {Mol Immunol}, keywords = {3-30, 3-33, d, rhesus, usage, v-gene}, month = {January}, number = {4}, pages = {412--422}, posted-at = {2007-06-04 06:50:30}, priority = {2}, title = {Extensive restrictions in the VH sequence usage of the human antibody response against the Rhesus D antigen.}, url = {http://dx.doi.org/10.1016/j.molimm.2006.02.021}, volume = {44}, year = {2007} }

TY - JOUR ID - citeulike:1361549 L3 - citeulike-article-id:1361549 N2 - Anti-Rhesus D immunoglobulin purified from human sera is used as a prophylactic reagent in Rhesus D negative women at risk of alloimmunization during pregnancy. We are currently developing a Rhesus D antigen-specific recombinant polyclonal antibody drug lead for replacing the existing blood derived-products. By analyzing the RhD-specific antibody VH repertoires from eight alloimmunized women we found, in agreement with previous studies, a strong preference for the VH 3-33 "superspecies" gene segments which encompasses the IGHV3-30-3*01, IGHV3-30*18, and IGHV3-33*01 VH alleles. Even more extensive genetic restriction was observed among five donors, which produced antibodies of identical V-D-J usage and CDR3 loop length and joining regions of similar amino acid composition. In addition, we find a high degree of sequence relatedness to previously isolated anti-Rhesus D antibodies. Such close homology in VH domains indicates that significant structural restrictions are operating in the selection of antibodies recognizing RhD as seen for T cell receptors. Moreover, some VH domains were isolated in their germline configuration indicating that anti-RhD antibodies of relatively high affinity are present in the naïve antibody repertoire of Rhesus negative individuals which offers an explanation for the strong and clinically significant immunogenicity of the Rhesus D. IS - 4 JF - Mol Immunol SN - 0161-5890 AD - Symphogen A/S, Elektrovej, Building 375, 2800 Lyngby, Denmark. psa@symphogen.com EP - 422 TI - Extensive restrictions in the VH sequence usage of the human antibody response against the Rhesus D antigen. VL - 44 SP - 412 KW - 3-30 KW - 3-33 KW - d KW - rhesus KW - usage KW - v-gene AU - Andersen, PS AU - Haahr-Hansen, M AU - Coljee, VW AU - Hinnerfeldt, FR AU - Varming, K AU - Bregenholt, S AU - Haurum, JS PY - 2007/01// UR - http://dx.doi.org/10.1016/j.molimm.2006.02.021 ER -