Ig VH-dependent interaction between immunoglobulins and CD4.

CD4 interacts with the immunoglobulin (Ig)-VH domains by a virtue of its solvent-exposed C and C strands. These two strands also contribute to the full HIV-gp120 binding and participate significantly in binding to class II MHC molecules. In this paper we hypothesize that any high-affinity interaction between serum (or membrane-expressed) Ig and CD4 may have impact on early T cell activation events. The existing data provide evidence for different outcomes of a high affinity Ig/CD4 interaction on T cell proliferation and cytokine secretion: costimulation and inhibition. We will also discuss how a low affinity CD4/Ig interaction could play an important role in B cell stimulation initiated through surface Ig receptors, and how CD4 may be involved in shaping the B cell repertoire.