pMHC Structural Comparisons as a Pivotal Element to Detect and Validate T-Cell Targets for Vaccine Development and Immunotherapy-A New Methodological Proposal

Cells. 2019 Nov 22;8(12):1488. doi: 10.3390/cells8121488.


The search for epitopes that will effectively trigger an immune response remains the "El Dorado" for immunologists. The development of promising immunotherapeutic approaches requires the appropriate targets to elicit a proper immune response. Considering the high degree of HLA/TCR diversity, as well as the heterogeneity of viral and tumor proteins, this number will invariably be higher than ideal to test. It is known that the recognition of a peptide-MHC (pMHC) by the T-cell receptor is performed entirely in a structural fashion, where the atomic interactions of both structures, pMHC and TCR, dictate the fate of the process. However, epitopes with a similar composition of amino acids can produce dissimilar surfaces. Conversely, sequences with no conspicuous similarities can exhibit similar TCR interaction surfaces. In the last decade, our group developed a database and in silico structural methods to extract molecular fingerprints that trigger T-cell immune responses, mainly referring to physicochemical similarities, which could explain the immunogenic differences presented by different pMHC-I complexes. Here, we propose an immunoinformatic approach that considers a structural level of information, combined with an experimental technology that simulates the presentation of epitopes for a T cell, to improve vaccine production and immunotherapy efficacy.

Keywords: cancer targets discovery; cellular immunology; immunotherapy targets; viral epitopes.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Epitopes / immunology
  • Humans
  • Immunotherapy*
  • Major Histocompatibility Complex / immunology*
  • Peptides / chemistry*
  • Peptides / immunology
  • Receptors, Antigen, T-Cell / immunology
  • Reproducibility of Results
  • T-Lymphocytes / immunology*
  • Viral Vaccines / immunology*


  • Epitopes
  • Peptides
  • Receptors, Antigen, T-Cell
  • Viral Vaccines