TCR-contacting residues orientation and HLA-DRβ* binding preference determine long-lasting protective immunity against malaria

Martha P. Alba, Carlos F. Suarez, Yahson Varela, Manuel A. Patarroyo, Adriana Bermudez, Manuel E. Patarroyo

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Fully-protective, long-lasting, immunological (FPLLI) memory against Plasmodium falciparum malaria regarding immune protection-inducing protein structures (IMPIPS) vaccinated into monkeys previously challenged and re-challenged 60 days later with a lethal Aotus monkey-adapted P. falciparum strain was found to be associated with preferential high binding capacity to HLA-DRβ1* allelic molecules of the major histocompatibility class II (MHC-II), rather than HLA-DRβ3*, β4*, β5* alleles. Complete PPIIL 3D structure, a longer distance (26.5 Å ± 1.5 Å) between residues perfectly fitting into HLA-DRβ1*PBR pockets 1 and 9, a gauche rotamer orientation in p8 TCR-contacting polar residue and a larger volume of polar p2 residues was also found. This data, in association with previously-described p3 and p7 apolar residues having gauche+ orientation to form a perfect MHC-II-peptide-TCR complex, determines the stereo-electronic and topochemical characteristics associated with FPLLI immunological memory.

Original languageEnglish (US)
Pages (from-to)654-660
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume477
Issue number4
DOIs
StatePublished - Sep 2 2016

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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