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The involvement of antigen processing in determinant selection by class II MHC and its relationship to immunodominance

The T cell response in vivo to many whole proteins is focused on a limited number of possible determinants which can be termed immunodominant. Antigen processing for class II antigen presentation appears to play a major role in this selective process. With experimental evidence accumulated in our laboratory as well as others, we review several possible mechanisms involved in antigen processing responsible for selective or differential determinant expression. In particular, we discuss the determinant capture model in which MHC class II molecules initially capture large antigen fragments, such that bound determinants are protected from proteolysis by the MHC molecules and eventually become dominant while the flanking determinants are trimmed away. Such flanking determinants therefore become subdominant or cryptic. This mechanism underlies the capturing role of MHC molecules in the physiological processing of antigens.