In the murine system we have demonstrated that selective recognition by recirculating lymphocytes of specialized high endothelial venules (HEV) mediates their exit from the blood into certain lymphoid tissues. Thus, differential expression by distinct lymphocyte subsets of """"""""receptors"""""""" complementary either to determinants expressed on lymph node HEV or to those on Peyer's patch HEV directs migration in an organ-specific fashion, thereby influencing the local character of the immune response in these sites. We have described a monoclonal antibody, MEL-14, that recognizes an 80-kilodalton cell surface glycoprotein which appears to be the receptor for lymph node HEV and have described its regulated expression during antigen dependent/independent development of the immune system. Using a similar immunization/screening protocol, other antibodies, 9B5 and 1D1, have been developed which recognize a glycoprotein expressed on human lymphocytes that may be the human lymphocyte receptor(s) for HEV. Although they are basically similar, preliminary comparison of the developmental regulation of HEV binding and MEL-14/985-1D1 antigen distribution in mouse and man has revealed significant differences. Since the 9B5/1D1 antigen also is expressed on lymphocytes of two species of macaque, it is the long-term objective of this proposal to develop this primate system as a model of directed lymphocyte migration more relevant to the human system--especially with respect to expression of homing receptors in fetal development and the pathogenesis of AIDS. More specificially, we will: (1) employ our standard assays for lymphocyte adherence to frozen tissue sections in vitro and for short-term homing in vivo, along with lymphatic duct canulation, two color FACS analyses, and immunohistologic staining to establish and correlate the in vivo migratory specificities, in vitro HEV-binding properties, and level of 9B5-1D1 antigen cxpression on defined lymphocyte subsets during fetal development and in normal/AIDS-affected adults; (2) make a structural comparison of the 9B5/1D1 antigens on macaque and human lymphocytes by immunoprecipitation and affinity chromatography; and (3) begin to identify mechanisms which may control selective exit from lymph nodes and Peyer's patches by comparing the surface phenotypes of exiting cells with those of the resident population. (LB)
