SELF AND VIRAL PEPTIDES CAN INITIATE LYSIS BY AUTOLOGOUS NATURAL-KILLER-CELLS

Citation
O. Mandelboim et al., SELF AND VIRAL PEPTIDES CAN INITIATE LYSIS BY AUTOLOGOUS NATURAL-KILLER-CELLS, Proceedings of the National Academy of Sciences of the United Statesof America, 94(9), 1997, pp. 4604-4609
Citations number
39
Categorie Soggetti
Multidisciplinary Sciences
ISSN journal
00278424
Volume
94
Issue
9
Year of publication
1997
Pages
4604 - 4609
Database
ISI
SICI code
0027-8424(1997)94:9<4604:SAVPCI>2.0.ZU;2-3
Abstract
Natural killer (NK) cells are inhibited by specific allotypes of class I major histocompatibility complex ligands recognized by polymorphic inhibitory receptors (e.g,, NKIR1 and NKIR2), NK1- and NK2-specific cl ones recognize two groups of HLA-C allotypes that are distinguished by a dimorphism at residue SO in the alpha 1 helix (alpha Lys-80 and alp ha Asn-80, respectively). ''Empty'' HLA-Cw7 expressed in peptide trans porter-deficient cells and HLA-Cw7 loaded with several peptides each f unctioned as inhibitory ligands for NK2 lines and clones. However, loa ding of HLA-Cw7 with two other peptides derived from glutamic acid dec arboxylase or coxsackie virus (each of which has been associated with autoimmune diabetes mellitus) abrogated this inhibitory recognition. B oth peptides contained LJ's at P8 of the epitope. Substitution of P8 w ith Ala or two other basic amino acids, His and Arg, resulted in pepti des that were inhibitory, as were peptides with P8 Val, Glu, or Asn, T he manner in which a Lys at PS might affect recognition is discussed, together with a hypothesis for a novel mechanism by which an autoimmun e disease might be initiated.