H19, a surface membrane molecule involved in T-cell activation, inhibits channel formation by human complement.
Here we compare the properties of leukocyte antigens H19 and CD59 with those of the PI-linked 18,000-20,000 Mr molecules which inhibit lysis of human cells by the autologous terminal complement components C5b-9. H19, a 19,000 Mr protein found on human erythrocytes, monocytes, neutrophils, T-lymphocytes and other cells, is one of the ligands involved in the spontaneous rosette formation between human T-lymphocytes and erythrocytes. Recent evidence indicates that H19 also participates in T-cell activation. CD59 is a widely distributed 18,000-25,000 Mr protein anchored to the cell membrane by phosphatidylinositol (PI). The function of CD59 is unknown. Affinity-purified H19 incorporates into cell membranes and inhibits channel formation by human C5b-9 on guinea pig erythrocytes. Significant inhibition is achieved with picogram quantities of H19, corresponding to approximately 600 molecules per erythrocyte. H19 is most effective when C9 is limiting but quite active when C5b-7 or C8 are limiting, indicating that it may interact with several of the structurally related terminal complement components. The inhibitory activity is blocked by mAbs to either CD59 or to H19. H19 is PI-anchored: it is released from the cell membrane by treatment with PI-specific phospholipase C, and it is absent from cells from a patient with paroxysmal nocturnal hemoglobinuria (PNH). Analysis of PNH erythrocytes after treatment with terminal complement proteins shows that the H19-negative erythrocytes are more susceptible to C5b-9-mediated lysis. Treatment of normal human erythrocytes with either anti-H19 or anti-CD59 renders them more susceptible to lysis by human C5b-9. We conclude that H19 and CD59 are probably the same molecule and are identical or closely related to the recently described inhibitors of C5b-9 channel formation.
Whitlow
M B
MB
Department of Dermatology, New York University School of Medicine, New York.
Iida
K
K
Stefanova
I
I
Bernard
A
A
Nussenzweig
V
V
D000911:Antibodies, Monoclonal / Q000276:immunology; D000943:Antigens, Differentiation / Q000276:immunology / Q000502:physiology*; D000954:Antigens, Surface / Q000276:immunology / Q000502:physiology*; D018957:CD59 Antigens; D003182:Complement C5 / Q000037:antagonists & inhibitors*; D050776:Complement C5b; D003186:Complement C9 / Q000037:antagonists & inhibitors*; D003169:Complement Inactivator Proteins / Q000502:physiology*; D006457:Hemoglobinuria, Paroxysmal / Q000097:blood; D006461:Hemolysis; D008213:Lymphocyte Activation; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D000954:Antigens, Surface; D018957:CD59 Antigens; D003182:Complement C5; D003186:Complement C9; D003169:Complement Inactivator Proteins; D050776:Complement C5b