Targeting Intracellular Antigens with pMHC-Binding Antibodies: A Phage Display Approach
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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 a phage display approach for the rapid generation of such antibodies with high specificity and affinity.
Key wordsPhage display Phage Human leukocyte antigen Major histocompatibility complex Antibody Protein expression Fc-fusion protein Single-chain variable fragment scFv T-cell receptor Peptide MHC
- 6.Luzzago A, Felici F, Tramontano A, Pessi A, Cortese R (1993) Mimicking of discontinuous epitopes by phage-displayed peptides, I. Epitope mapping of human H ferritin using a phage library of constrained peptides. Gene 128:51–57. https://doi.org/10.1016/0378-1119(93)90152-S CrossRefPubMedGoogle Scholar
- 17.Liu H et al (2016) Targeting alpha-fetoprotein (AFP)-MHC complex with CAR T cell therapy for liver cancer. Clin Cancer Res. https://doi.org/10.1158/1078-0432.ccr-16-1203