TY - JOUR AU - Kearns-Jonker, Mary AU - Barteneva, Natasha AU - Mencel, Robert AU - Hussain, Namath AU - Shulkin, Irina AU - Xu, Alan AU - Yew, Margaret AU - Cramer, Donald V. PY - 2007 DA - 2007/03/12 TI - Use of molecular modeling and site-directed mutagenesis to define the structural basis for the immune response to carbohydrate xenoantigens JO - BMC Immunology SP - 3 VL - 8 IS - 1 AB - Natural antibodies directed at carbohydrates reject porcine xenografts. They are initially expressed in germline configuration and are encoded by a small number of structurally-related germline progenitors. The transplantation of genetically-modified pig organs prevents hyperacute rejection, but delayed graft rejection still occurs, partly due to humoral responses. IgVH genes encoding induced xenoantibodies are predominantly, not exclusively, derived from germline progenitors in the VH3 family. We have previously identified the immunoglobulin heavy chain genes encoding VH3 xenoantibodies in patients and primates. In this manuscript, we complete the structural analysis of induced xenoantibodies by identifying the IgVH genes encoding the small proportion of VH4 xenoantibodies and the germline progenitors encoding xenoantibody light chains. This information has been used to define the xenoantibody/carbohydrate binding site using computer-simulated modeling. SN - 1471-2172 UR - https://doi.org/10.1186/1471-2172-8-3 DO - 10.1186/1471-2172-8-3 ID - Kearns-Jonker2007 ER -