A New Strategy for Mapping Epitopes of LACK and PEPCK Proteins of Leishmania amazonensis Specific for Major Histocompatibility Complex Class I

Int J Mol Sci. 2023 Mar 22;24(6):5972. doi: 10.3390/ijms24065972.

Abstract

Leishmaniasis represents a complex of diseases with a broad clinical spectrum and epidemiological diversity, considered a major public health problem. Although there is treatment, there are still no vaccines for cutaneous leishmaniasis. Because Leishmania spp. is an intracellular protozoan with several escape mechanisms, a vaccine must provoke cellular and humoral immune responses. Previously, we identified the Leishmania homolog of receptors for activated C kinase (LACK) and phosphoenolpyruvate carboxykinase (PEPCK) proteins as strong immunogens and candidates for the development of a vaccine strategy. The present work focuses on the in silico prediction and characterization of antigenic epitopes that might interact with mice or human major histocompatibility complex class I. After immunogenicity prediction on the Immune Epitope Database (IEDB) and the Database of MHC Ligands and Peptide Motifs (SYFPEITHI), 26 peptides were selected for interaction assays with infected mouse lymphocytes by flow cytometry and ELISpot. This strategy identified nine antigenic peptides (pL1-H2, pPL3-H2, pL10-HLA, pP13-H2, pP14-H2, pP15-H2, pP16-H2, pP17-H2, pP18-H2, pP26-HLA), which are strong candidates for developing a peptide vaccine against leishmaniasis.

Keywords: H2Db; HLA; MHC I; T epitopes; bioinformatics; cutaneous leishmaniasis; peptides; tetramer; vaccine.

MeSH terms

  • Animals
  • Epitopes
  • HLA Antigens
  • Histocompatibility Antigens Class I
  • Humans
  • Leishmania mexicana*
  • Leishmania* / metabolism
  • Leishmaniasis, Cutaneous*
  • Major Histocompatibility Complex
  • Mice
  • Peptides / chemistry
  • Vaccines, Subunit

Substances

  • Epitopes
  • Histocompatibility Antigens Class I
  • HLA Antigens
  • Peptides
  • Vaccines, Subunit