NK3-specific natural killer cells are selectively inhibited by Bw4-positive HLA alleles with isoleucine 80.

Abstract

SummaryNatural kiUer (NK) cell dones have been previously described which are inhibited by HLA-C aUdes with Asn77-LysS0 (NKl-specific cdls) or by HLA-C alldes with Ser77-Asn80 (NK2-specific ceils). In the present work, the generation of NK cells with HLA-B-rdated spedficities was attempted by stimulation of a Bw4 homozygous responder by a Bw6 homozygous donor. Two NK clones were found, which were inhibited by HLA-Bw4 (but not by HLA-Bw6) allotypes and by some HLA-A allotypes that share the Bw4 public epitope. Inhibition of NK cell-mediated lysis strongly correlated with the presence of an Ile residue at position 80 of the protective allele. These NK cdl dones define a new specificity termed NK3.

Deciphering the killer‐cell immunoglobulin‐like receptor system at super‐resolution for natural killer and T‐cell biology

“…35, 114, 115 Recognition of Bw4 by KIR3DL1 is sensitive to polymorphism both within and outside the Bw4 motif, as well as to the sequence of the bound peptide 42, 63, 116, 117, 118. Early work showed that HLA‐Bw4 allotypes with I80 formed more potent ligands for KIR3DL1 than those with T80,119 a functional difference reinforced by associations with disease outcome 27, 58, 120, 121, 122. However, recent high‐resolution studies have identified several I80 Bw4 allotypes that are poorly recognized by KIR3DL1, providing weaker KIR3DL1 ligands than selected T80 Bw4 allotypes 39, 41, 123.…”

Combination of KIR and HLA gene variants augments the risk of developing birdshot chorioretinopathy in HLA-A*29-positive individuals

“…In contrast, the reciprocal association displaying increased frequencies of C2/C2 and Bw6/Bw6 homozygotes was observed in HLA-A*29-negative controls. Over 75% of the patients and HLA-A*29 PC carried the subset of Bw4 allotypes containing threonine 80 (Bw4 T80 ), which provides weaker inhibition than Bw4 containing isoleucine at this position (Bw4 I80 ) 23,53 (Table 2). In contrast, most Bw4-positive individuals in the HLA-A*29 NC group carried the strongly inhibitory Bw4 I80 subset.…”

“…KIR2DL2 and 2DL3 bind a subset of HLA-C allotypes containing an asparagine at amino-acid position 80 of the heavy chain (HLA-C1 alleles) and KIR2DL1 binds the remaining HLA-C allotypes with lysine 80 (HLA-C2 alleles). [19][20][21] KIR3DL1 binds 40% of the HLA-B allotypes containing a serologically defined Bw4 epitope 22,23 and KIR3DL2 binds HLA-A3/A11. 24,25 The strength of these interactions is highly sensitive to polymorphism of the KIR and HLA genes, as well as the HLA-bound peptide sequence.…”

Crystal structures and KIR3DL1 recognition of three immunodominant viral peptides complexed to HLA‐B*2705

“…Evidence indicates that KIR3DL1 binds the MHC a1 helix around residues 76-80, with specificity for all Bw4 alleles containing threonine at heavy-chain residue 80 [17]. In the case of HLA-B*2705 at least, KIR3DL1 also has specificity for bound peptide, showing greatest sensitivity for the residue at position 8 [18][19][20].…”