TCR Targets Validation Through T Cell Activation

In this webinar sponsored by GenScript, Dr. Anna Pasetto, Assistant Professor, Department of Laboratory Medicine, Karolinska Institutet, discussed current approaches to validating TCR targets for cancer immunotherapy, including limitations and key opportunities for improvement.

In the context of her work, Dr. Pasetto’s talk focused specifically on αβ T cells, including two major subgroups, CD8⁺ and CD4⁺ T cells, which interact specifically with peptides presented by the human leukocyte antigen (HLA) class I and class II complexes, respectively. The specificity of the T cell receptor (TCR)-antigen interaction is dependent on the peptide sequence in the context of the HLA complex. CD8⁺ and CD4⁺ T cell antigens may be leveraged as targets for cancer immunotherapy. Ideally, peptide targets for T cell-based cancer immunotherapy should be highly immunogenic and uniquely expressed at high levels by all tumor cells.

T cell-targeted antigens differ in their presentation by HLA class I and class II complexes. HLA class I presented peptides consist of ~8-12 a.a. and originate from intracellular antigens, while HLA class II peptides are longer consisting of ~12-18 a.a. and originate from extracellular antigens. Intracellular proteins provide more opportunities for T cell target identification.