The movement of lymphocytes from the blood into secondary lymphoid organs and back to the blood again is known as lymphocyte recirculation. This process is an important component of immune surveillance, as it facilitates the exposure of the body's repertoire of lymphocyte specificities to sequestered and processed antigens in the lymphoid organs. In certain diseases the migration of lymphocytes into inappropriate compartments (i.e, joint synovia during rheumatoid arthritis) leads to tissue damage. The overall objective of our research is to understand the biochemical mechanisms involved in the attachment of blood- borne lymphocytes to specialized high endothelial venules (HEV) found in secondary lymphoid organs. This highly specific cell-cell recognition event, which is dependent on both lymphocyte type and the anatomic site of the HEV, initiates the extravasation of normal lymphocytes from the blood into the parenchyma of lymphoid organs and may also determine the dissemination sites of lymphoid malignancies. Our previous work has established that lymphocytes express a cell surface carbohydrate-binding receptor (CBR) that participate in the attachment of lymphocyte to HEV in peripheral lymph nodes (i.e., """"""""lymphocyte homing receptor""""""""). Also we established that the lymphocyte attachment sites on PN HEV require sialic acid for their activity. The major objectives of our proposed research are: 1) to determine the relationship between the CBR and the MEL-14 antigen, a 80 kDa glycoprotein previously implicated in lymphocyte homing; 2) to determine the relationship between a soluble lymph factor with specific HEV- binding activity and the CBR; 3) to identify the linkage of sialic acid required for the activity of PN HEV attachment sites; 4) to identify the actual attachment sites for lymphocytes on PN HEV and PP HEV; and 5) to identify the homing receptor that mediates attachment of lymphocytes to HEV in Peyer's patches, a gutassociated lymphoid organ.
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