August 14, 1959

Dr. Emil Le. Smith

Department of Blochemistry
University of Utah School of Medicine
Salt Lake Clty, Utah

Dear Emil:

what would you say to the guess that the specific carbohydrate
you are finding In globulin is the specific receptor for complement?
Complement fixation has always puzzled me since It did not easily make
sense that it should depend on the Interaction between antibedy and anticen
but the nature of the antigen was immaterial. &8ut suppose it Is some
common element fin af! ontibody which recognizes complement but the
binding energy cf a single antibody molecule wlth complemert Is Insufficient
to make a stable complex. However, complexes consisting cf at least
2 antibecy molecules stabilized by their reaction with a common antigen,
might then have the further capacIty to bind complement between them.
If there is such a common element among al! antibodies, it seemed to me
thet your carbohydrate might be a plausible candidate. Complement then
becomes a sort of antibody to the globulIn-carbohydrate; perhaps further,
the same carbohydrate or a re!ated one Is the cell-wall-element which fs
the substrate for the enzymatic action of complement. Anyhow, If you
haven't already done this, the hunch does suggest one of a great many
tests tc make on the carbohydrate fraction. Another point that might
be pertinent | am not clear on: the extent of fixation cf complement
by soluble antigen-antibody complexes where the postulated condition
of two adjacent antibody molecules would not be met.

Yours sincerely,

Joshua Lederberg

Encl.