Biochemical and Biophysical Research Communications, Vol.477, No.4, 654-660, 2016
TCR-contacting residues orientation and HLA-DR beta* binding preference determine long-lasting protective immunity against malaria
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-DR beta 1* allelic molecules of the major histocompatibility class II (MHC-II), rather than HLA-DR beta 3*, beta 4*, beta 5* alleles. Complete PPIIL 3D structure, a longer distance (26.5 angstrom +/- 1.5 angstrom) between residues perfectly fitting into HLA-DR beta 1*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. (C) 2016 Elsevier Inc. All rights reserved.