Targeting Intracellular Antigens with pMHC-Binding Antibodies: A Phage Display Approach

Antibodies that bind peptide-MHC (pMHC) complex in a manner akin to T cell receptor (TCR) have not only helped in understanding the mechanism of TCR-pMHC interactions in the context of T cell biology but also spurred considerable interest in recent years as potential cancer therapeutics. Traditional methods to generate such antibodies using hybridoma and B cell sorting technologies are sometimes inadequate, possibly due to the small contribution of peptide to the overall B cell epitope space on the surface of the pMHC complex (typical peptide MW = 1 kDa versus MHC MW = 45 kDa) and to the multiple efficiency limiting steps inherent in these methods. In this chapter we describe phage display approaches, including a cell panning strategy, for the rapid generation of such antibodies with high specificity and affinity.