Generation of TCR-Like Antibodies Using Phage Display

Methods Mol Biol. 2015;1348:191-204. doi: 10.1007/978-1-4939-2999-3_17.


The adaptive immune response against cancer consists of two arms: the humoral response from B cells, and the cell-mediated response from T cells. The humoral response has the advantage of diversity, theoretically recognizing antigens of any type (sugar, protein, lipid, etc.), but is generally limited to surface-expressed targets. T cells on the other hand, can recognize intracellular targets, but only if they are proteins, and presented as small peptide fragments on major histocompatibility complex (MHC) cell surface antigens. However, with advances in protein engineering and phage display, it has become feasible to quickly identify and generate antibodies or single-chain variable fragments against peptide-MHC, thus bridging the two arms, and allowing for recognition, identification, and effector responses against cells expressing intracellular targets.

Keywords: Antibody; Fc-fusion protein; Human leukocyte antigen; Major histocompatibility complex; Peptide MHC; Phage; Phage display; Protein expression; Single-chain variable fragment; T-cell receptor; scFv.

MeSH terms

  • Cell Surface Display Techniques*
  • Epitopes, T-Lymphocyte / immunology
  • Gene Expression
  • Humans
  • Major Histocompatibility Complex / immunology
  • Peptide Library*
  • Peptides / immunology
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology*
  • Single-Chain Antibodies / chemistry
  • Single-Chain Antibodies / genetics
  • Single-Chain Antibodies / immunology*
  • T-Lymphocytes / immunology


  • Epitopes, T-Lymphocyte
  • Peptide Library
  • Peptides
  • Recombinant Fusion Proteins
  • Single-Chain Antibodies