UC Irvine

Lymphotoxins derived from activated lymphocytes from human and murine lymphoid cells are heterogeneous with respect to molecular size and charge, as well as with respect to the expression of carbohydrate residues. These molecules form a system of interrelated subunits, as evidenced by their shared antigenic determinants, as well as by the reversible dissociation of the smaller forms from the larger. Although the smaller molecular weight forms (αl, β, γ) are apparently only capable of relatively protracted lysis of selected strains of the murine L-929 cell, the higher molecular weight forms (Cx, αH) appear to be capable of rapid lysis of the L cell, as well as of relatively rapid, nonspecific lysis of other cells. Furthermore, the Cx forms appear to be associated with an antigen binding receptor which may be of T cell origin. Moreover, these forms released by alloimmune murine T cells can specifically lyse allogeneic tumor cells used in sensitization. The human Cx and αH LT also appear to express determinants encoded by genes of the MHC. Presently, we have been able to incorporate 125I into both human and murine lymphotoxin preparations, while fully preserving biological activity. This has enabled us to monitor our attempts at purification of these materials through several consecutive isolation procedures including molecular sieving, ion-exchange chromatography, lectin affinity chromatography, hydrophobic chromatography and electrophoresis. Our results indicate that these materials are present in lymphocyte supernatants in extremely small amounts, probably less than 25 ng/ml; thus the purification of each component by biochemical techniques will require very vigorous methods. © 1980.