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
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.