Organ xenografts under certain circumstances survive in the presence of anti-graft antibodies and complement, a situation referred to as "accommodation." We find that the endothelial cells (ECs) in hamster hearts that accommodate themselves in rats express genes, such as A20 and bcl-2, that in vitro protect ECs from apoptosis and prevent upregulation in those cells of proinflammatory genes such as cytokines, procoagulant and adhesion molecules. Hearts that are rejected do not express these genes. In addition, vessels of rejected hearts show florid transplant arteriosclerosis whereas those of accommodated hearts do not. Accommodated xenografts have an ongoing T helper cell type 2 (Th2) cytokine immune response, whereas the rejected grafts have a Th1 response. We propose a model for factors that contribute to the survival of xenografts and the avoidance of transplant arteriosclerosis.

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Antigenic determinants encoded by genes of the HLA-D region have been related to at least three separate molecular complexes, DR, MB (also known as DC and LB-E), and SB. At the cell surface each complex has a dimeric structure composed of a structurally conserved a-chain noncovalently associated with a polymorphic fl-chain. The DR and MB series of determinants have been extensively characterized using allospecific serological reagents and, to date, 10 DR and 3 MB allotypes are recognized. Beyond these serologically detectable polymorphisms, HLA-D region products exhibit an additional degree of antigenic complexity revealed by cellular reagents such as homozygous typing cells (HTC). These cells respond to antigenic determinants (Dw/LD determinants) that are phenotypically distinct from those recognized by available antisera. Thus, within a panel of individuals of a single serologically defined DR type, such as DR4, a number of different Dw/LD specificities including Dw4, Dwl0, DYT, DB3, and LD40 exist (1).In this report we have addressed this cellularly detected antigenic complexity from a molecular perspective. Using isoelectric focusing (IEF) to analyze DR molecules immunoprecipitated from a panel of individuals homozygous for DR4, but expressing different Dw/LD determinants, we have observed that (a) between DR4 fl-chains, but not a-chains, considerable structural polymorphism exists and (b) the particular DR fl-chain structural configuration observed upon IEF is associated with the cell Dw/LD type. These data, thus, provide the first molecular evidence associating the Dw/LD determinants recognized by cellular reagents to the serologically defined DR molecule. Materials and MethodsIdentification and Derivation of DR4 Lymphoblastoid Cell Lines. DR and Dw/LD typing was performed according to previously described methods (2, 3). Whole blood was obtained from healthy DR4, Dw/LD homozygous donors. After centrifugation on a Ficoll-Hypaque cushion, lymphocytes were macrophage depleted by plastic adherence and B cell enriched by rosettedepleting T cells with AET-treated sheep erythrocytes (4). LCL were established by infecting the B cell-enriched lymphocyte population with Epstein-Barr virus according to published procedures (5). LCL were maintained with RPMI 1640 containing 25 mM Hepes buffer and 10% heat-inactivated fetal bovine serum.Cell Labeling, Immunoprecipitation, and Two-dimensional Gel Analysis. LCL were cell-surfacelabeled by lactoperoxidase-catalyzed 125I-iodination and membrane proteins detergent-solubi-* Paper 326 from the