Retroviral Antibody Binding of the MHC Class II Molecule: A Biochemical Influence on CD4 T Cell Differentiation in HIV Infection?

Abstract

Retroviral antibody capable of binding to the major histocompatibility complex (MHC) Class II molecule has been documented in human immunodeficiency virus-1 (HIV-1)-infected patients. Interactions between the MHC Class II receptor and the T-cell receptor (TCR) are central to the immune response. Importantly, retroviral antibody possesses a much higher binding affinity for the MHC Class II receptor, when compared to the TCR. Experiments have manipulated a number of factors related to antigen-presenting cell (APC) interaction with differentiating T-cells. These studies have observed the effects of lowering antigen dose and reducing ligand density on precursor Th (T helper) cell differentiation. Studies have also examined the effect of downregulated MHC Class II receptors and co-stimulatory molecules on APC–Th cell interaction. In addition, the sequestration of antigens away from the Class II processing pathway has been studied. These investigations reveal a general trend that can determine whether a naive CD4 T-cell becomes a Th1 or Th2-like cell. If the experimental manipulation weakens the APC-Th cell interaction, a weak ligating TCR signal results. Consequently, a weak ligating TCR signal can influence precursor Th cells to become Th2-like cells. Retroviral antibody binding of MHC Class II receptors may mimic a number of experimental conditions responsible for creating a weak ligating TCR signal.