Which immunoglobulin class is most commonly involved in type II hypersensitivity reactions against cell-surface antigens?

• A. IgM
• B. IgG
• C. IgA
• D. IgE

Answer: (B)

Type II hypersensitivity is a cytotoxic reaction driven by antibodies binding to antigens on the surface of cells, which then activates complement or promotes phagocytosis and sometimes NK-cell–mediated killing. The immunoglobulin class most commonly responsible for this process is IgG. IgG is the predominant serum antibody and can access tissues, bind to cell-surface antigens, and engage Fc receptors on phagocytes and NK cells, initiating opsonization, antibody-dependent cellular cytotoxicity, and classical complement activation that leads to target cell destruction. While IgM can also mediate type II reactions, especially against soluble or highly repetitive antigens like ABO blood group antigens (which often cause rapid intravascular hemolysis), the typical cell-surface antigen–directed cytotoxic responses are driven by IgG. IgA and IgE do not play major roles in type II hypersensitivity.