Role for the third constant domain of the IgG H chain in activation of complement in the presence of C1 inhibitor.
The multidomain architecture of Ig H chains was initially implicated in the variety of functions imposed on each species of Ig. However, the activation of C by IgG is the only function that has been attributed to a single domain of C gamma 2, whereas most of other functions of IgG require both C gamma 2 and C gamma 3 domains. This one domain-one function relationship in the C activation by IgG, too, was questioned recently by the fact that a C gamma 3-less fragment of rabbit IgG, F(acb)2, is definitely less capable of activating C than intact IgG. Here we reexamined capacities of F(acb)2 to bind and activate C1 in the presence and absence of C1 inhibitor (C1-In) in comparison with intact IgG, by using SRBC sensitized with these proteins (EFacb, EIgG). At an ionic strength of 0.065 and 37 degrees C, where C1q was bound equally well by these cells and the dissociation was limited, C1s, presumably in the form of C1r2C1s2, dissociated from EFacb at a rate 7-fold greater than that from EIgG, irrespective of the presence or absence of C1-In. A physiologic concentration of C1-In reduced the rate of C1 activation by EFacb to 5% that by EIgG. The results present evidence that the C gamma 3 domain, too, plays a crucial part in the C1 activation process by stabilizing the zymogenic conformation of C1 and protecting it from the attack by C1 inhibitor.
Okada
M
M
Department of Microbiology, Ehime University School of Medicine, Japan.
Utsumi
S
S
D000818:Animals; D003167:Complement Activation / Q000187:drug effects; D003172:Complement C1 / Q000378:metabolism; D003174:Complement C1 Inactivator Proteins / Q000502:physiology*; D003173:Complement C1s / Q000378:metabolism; D006801:Humans; D007127:Immunoglobulin Constant Regions / Q000502:physiology*; D007140:Immunoglobulin Fab Fragments / Q000502:physiology; D007141:Immunoglobulin Fc Fragments / Q000502:physiology; D007074:Immunoglobulin G / Q000502:physiology*; D007143:Immunoglobulin Heavy Chains / Q000502:physiology*; D011817:Rabbits; D012756:Sheep
D003172:Complement C1; D003174:Complement C1 Inactivator Proteins; D007127:Immunoglobulin Constant Regions; D007140:Immunoglobulin Fab Fragments; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D003173:Complement C1s