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The 'dangerous liaison' between CD4 and gp120 that offers the first entry opportunity to HIV may also provoke perturbations of the immune control of the host with far-reaching immunopathological consequences. We wondered whether a mechanism of intermolecular help (T help across the gap of a non-covalent bond, in contrast to the intramolecular help of carrier to hapten) could break self-tolerance and be the cause of the frequent anti-CD4 autoantibodies found in AIDS patients. To determine whether this hypothesis deserves further testing, we designed a series of in vitro and in vivo experiments of increasing complexity, focused on the presentation of gp120 to specific T cells by antigen presenting cells (APC) exposed to the envelope protein in the form of non-covalent complexes. Bi-molecular complexes were constructed by allowing gp120 or gp160 to bind specific human mAbs. Tri-molecular complexes were constructed by introducing CD4 as an intermediate ligand between gp120 and mouse mAbs specific for CD4. In all cases the use of complexes did enhance the immunogenic capacity of substimulatory doses of gp120 or gp160 by facilitating uptake by APC via Fc receptor and consequent presentation to specific human T cell clones. Finally, help for the production in vivo of anti-CD4 antibodies was obtained from T lymphocytes specific for gp120 when CD4-primed memory B cells were pulsed with CD4 complexed with gp120, thus demonstrating in the mouse the entire cycle of intermolecular help via non-covalent interaction, and setting the stage for future experiments on self-tolerance breakage in a human molecular context.

PLATES 90 AND 91(Received for publication 18 December 1967) Infections occurring in utero or shortly after birth can have manifestations extending throughout the life-span of the affected organism. These manifestations range from stunted growth or malformations to immunological paralysis or infection immunity. It will be shown in the present paper that a lasting depression of weight can be readily and consistently induced by contaminating specific-pathogen-fred mice shortly after their birth with an agent derived from the intestinal tract of so-called "normal" mice.The phrase "normal mice" is used here to denote animals that have been raised under ordinary conditions and appear healthy. The weight-depressing agent ~ to be discussed in this paper has been recovered from the three colonies of ordinary albino mice tested for its presence. As it can be readily transmitted by contact to newborn mice of certain SPF colonies without causing in them any obvious disease other than weight depression, such experimental transfer will be referred to as contamination rather than infection.The transfer of the growth-depressing effect was first observed 5 yr ago while comparing the characteristics of two related mouse colonies, both of them maintained at that time in our laboratory (2). Animals of the Standard Swiss (SS) colony were produced on a large scale without any special precaution, whereas the animals of the NCS colony which had been derived from SS as described in preceding papers (1) were maintained under protected conditions. Despite their common origin, the SS and NCS mice differed in many char-* These studies were supported (in part)

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