What must be recognized for antigen presentation to occur on a cell's surface?

• A. Soluble antigens circulating in plasma
• B. Any protein bound to antibodies
• C. A specific antigen-MHC protein combination on a cell's plasma membrane
• D. A lipid antigen bound to CD1

Answer: (C)

Antigen presentation on the cell surface requires displaying a processed antigen bound to an MHC molecule. The T cell receptor recognizes this specific antigen–MHC combination, not free antigen. In APCs, peptides are generated from proteins and loaded into MHC grooves, then sent to the plasma membrane where CD4+ helper T cells (via MHC class II) and CD8+ cytotoxic T cells (via MHC class I) can see them. Soluble antigens circulating in plasma aren’t recognized by T cells until they’re processed and presented in this way. Lipid antigens can be presented by CD1 molecules to a specialized T cell subset, but the classic and most general requirement for surface presentation is the antigen bound to an MHC molecule.