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KIR3DL1 and HLA-A and HLA-B Peptide-Dependent Interactions Between Cutting Edge: Allele-Specific

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KIR3DL1 and HLA-A and HLA-B Peptide-Dependent Interactions Between Cutting Edge: Allele-Specific Cutting Edge: Allele-Specific and Peptide-Dependent Interactions between KIR3DL1 and HLA-A and HLA-B This information is current as Hathairat Thananchai, Geraldine Gillespie, Maureen P. of September 29, 2021. Martin, Arman Bashirova, Nobuyo Yawata, Makoto Yawata, Philippa Easterbrook, Daniel W. McVicar, Katsumi Maenaka, Peter Parham, Mary Carrington, Tao Dong and Sarah Rowland-Jones J Immunol 2007; 178:33-37; ; Downloaded from doi: 10.4049/jimmunol.178.1.33 http://www.jimmunol.org/content/178/1/33 References This article cites 28 articles, 12 of which you can access for free at: http://www.jimmunol.org/ http://www.jimmunol.org/content/178/1/33.full#ref-list-1 Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists by guest on September 29, 2021 • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2007 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. THE JOURNAL OF IMMUNOLOGY CUTTING EDGE Cutting Edge: Allele-Specific and Peptide-Dependent Interactions between KIR3DL1 and HLA-A and HLA-B1,2 † ‡ Hathairat Thananchai,* Geraldine Gillespie,* Maureen P. Martin, Arman Bashirova,ʈ Nobuyo Yawata,§ Makoto Yawata,§ Philippa Easterbrook,¶ Daniel W. McVicar, Katsumi Maenaka,# Peter Parham,§ Mary Carrington,† Tao Dong,3,4* and Sarah Rowland-Jones3,4* ؉ Although it is clear that KIR3DL1 recognizes Bw4 transmembrane proteins comprising two (KIR2D) or three ؉ HLA-B, the role of Bw4 HLA-A allotypes as KIR3DL1 (KIR3D) extracellular Ig-like domains. In general, KIRs with long cytoplasmic tails (KIR2DL and KIR3DL) transduce an in- ligands is controversial. We therefore examined the bind- Downloaded from ing of tetrameric HLA-A and –B complexes, including hibitory signal to inhibit NK cell lysis, whereas KIRs with short ؉ HLA*2402, a common Bw4 HLA-A allotype, to cytoplasmic tails (KIR2DS and KIR3DS) activate NK cell KIR3DL1*001, *005, *007, and *1502 allotypes. Only function (5, 6). An exception is KIR2DL4, the HLA-G recep- ؉ Bw4 tetramers bound KIR3DL1. Three of four HLA- tor, which combines a long cytoplasmic tail with activating A*2402 tetramers bound one or more KIR3DL1 allotypes function (7). and all four KIR3DL1 allotypes bound to one or more KIR2D recognizes HLA-C determinants, whereas KIR3D http://www.jimmunol.org/ HLA-A*2402 tetramers, but with different binding spec- receptors recognize HLA-A and -B alleles (5). Polymorphisms ␣ ificities. Only KIR3DL1*005 bound both HLA-A*2402 in the C terminus of the HLA class I 1 helix (residues 77–83) and HLA-B*5703 tetramers. HLA-A*2402-expressing strongly influence KIR interactions. For HLA-A and -B this is target cells were resistant to lysis by NK cells expressing also the site of the serological Bw4 and Bw6 epitopes and their KIR3DL1*001 or *005. This study shows that HLA- corresponding sequence motifs (8). KIR3DL1 specificity was A*2402 is a ligand for KIR3DL1 and demonstrates how originally defined in cellular assays that examined the ability of ؉ different HLA class I molecules to protect targets from NK cell the binding of KIR3DL1 to Bw4 ligands depends upon lysis. In one such analysis of NK clones Cella et al. (9) found by guest on September 29, 2021 the bound peptide as well as HLA and KIR3DL1 ϩ that both Bw4 HLA-A and -B allotypes were inhibitory; they polymorphism. The Journal of Immunology, 2007, 178: emphasized the strong, but incomplete, correlation with the 33–37. presence of isoleucine 80 (I80). In contrast, the analysis of NK cell clones from other donors by Gumperz et al. (10) correlated ϩ atural killer cells represent a major component of in- inhibition with Bw4 HLA-B allotypes irrespective of the po- ϩ nate immunity; they can kill tumor or virus-infected sition 80 residue and found no interaction with two Bw4 cells without prior sensitization and play an impor- HLA-A allotypes, A*2501 and A*2403. Subsequent compari- N ϩ tant role in the control of virus infections (1, 2). NK lysis is son of five HLA-B27 subtypes (all Bw4 ) showed that the four inhibited when their inhibitory receptors interact with class I subtypes with threonine 80 (B*2701, *2703, *2704, *2705, HLA molecules on target cells. Receptors for the classical and *2706) were strong inhibitors of NK cells, whereas the one HLA-A, -B, and -C molecules are encoded by genes in the killer subtype with I80 (B*2702) did not inhibit (11). The molecular cell Ig-like receptor (KIR)5 gene complex (3, 4); like HLA-A, B basis for these functional differences was not determined and and C, the KIR genes are highly polymorphic. KIRs are type I while there has been increasing evidence for KIR3DL1 interactions *Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular tute, National Institutes of Health under Contract N01-CO-12400. H.T. was funded by Medicine, Oxford, United Kingdom; †Laboratory of Genomic Diversity, Science Appli- the Royal Thai Government. cations International Corporation-Frederick, National Cancer Institute, Frederick, MD 2 The content of this publication does not necessarily reflect the views or policies of the 21702; ‡Johns Hopkins University School of Medicine, Baltimore, MD 21205; §Depart- Department of Health and Human Services, nor does mention of trade names, commercial ment of Structural Biology and Department of Microbiology and Immunology, Stanford products, or organizations imply endorsements by the U.S. government. University School of Medicine, Stanford, CA 94305; ¶Department of HIV/Genitourinary Medicine, The Guy’s, Kings’, and St. Thomas’ School of Medicine, London, United King- 3 T.D. and S.R.-J. contributed equally to this work. dom; ʈLaboratory of Experimental Immunology, National Cancer Institute, Frederick, 4 Address correspondence and reprint requests to Dr. Tao Dong and Dr. Sarah Rowland- MD 21702; and #Division of Structural Biology, Medical Institute of Bioregulation, Jones, Medical Research Council Human Immunology Unit, Weatherall Institute of Mo- Kyushu University, Fukuoka, Japan lecular Medicine, John Radcliffe Hospital, Oxford OX3 9DS, United Kingdom. E-mail Received for publication May 19, 2006. Accepted for publication October 17, 2006. addresses: [email protected] and [email protected] The costs of publication of this article were defrayed in part by the payment of page charges. 5 Abbreviations used in this paper: KIR, killer Ig-like receptor; LTNP, long-term nonpro- This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. gressor; rh, recombinant human. Section 1734 solely to indicate this fact. 1 This work was funded by the Medical Research Council, United Kingdom and in part with federal funds under the Intramural Research Program of the National Cancer Insti- www.jimmunol.org 34 CUTTING EDGE: SPECIFIC BINDING OF HLA CLASS I MOLECULE TO KIR3DL1 ϩ ϩ with Bw4 HLA-B, the significance of interactions with Bw4 lysis was calculated using the following formula: percentage specific lysis ϭ ϫ Ϫ Ϫ HLA-A (which all have I80) remains uncertain. 100% [(experimental lysis spontaneous lysis)/(maximum lysis sponta- neous lysis)]. A possible cause of the differences observed in the HLA-A and -B specificity of KIR3DL1 is genetic polymorphism of KIR3DL1 genotyping KIR3DL1, which we now know is extensive (12–14) but was Genomic DNA was isolated from PBMCs using the PureGene DNA isolation not appreciated at the time of the earlier studies (9–11). Thus, kit (GentraSystems). Following PCR, KIR3DL1 was sequenced using the fol- Ј Ј the NK cell clones may well have expressed different forms of lowing primers: exon 3, 5 -TTCTTGGTCCAGAGGGCCGGT-3 (forward) and 5Ј-CTGTGACCATGATCACCAC-3Ј (reverse); exon 4, 5Ј-GAAACCA KIR3DL1, potentially with different HLA class I specificities. CAGAAAACCTTCCC-3Ј (forward) and 5Ј-AGAGAGAAGGTTTCTCA To address this question, we used well-defined peptide-HLA TATG-3Ј (reverse); exon 5, 5Ј-GCCTCTTCTCCTTCCAGGTCC-3Ј (for- class I tetrameric complexes (“tetramers”) to dissect the inter- ward) and 5Ј-CACCTGTGACAGAAACAAG-3Ј (reverse); exons 7–9, 5Ј- AGTGGTCATCATCCTCTTCATC-3Ј (forward) and 5Ј-GTGTACAAGA actions between polymorphic variants of KIR3DL1 and TGG TATCTGTA-3Ј (reverse). Cycle sequencing was performed using the HLA-A and -B. ABI BigDye terminator cycle sequencing ready reaction kit (Applied Biosys- tems) and samples were run on an ABI 3730xl sequencer. Materials and Methods Generation of NK clones Results and Discussion We previously used HLA class I tetramers to show that PBMCs were obtained from laboratory workers and members of a previously KIR3DL2 specificity depends upon both the MHC class I mol- described HIV-1-infected, long-term nonprogressor (LTNP) cohort (ethically ecule, either HLA-A3 or –A11, and a specific bound peptide de- approved by the Research Ethics Committee of King’s College Hospital, Lon- Downloaded from don, U.K.) (15). NK cells were negatively selected using anti-CD3, anti-CD14, rived from the EBV (17). We used a similar strategy to investigate and anti-CD19-coated magnetic beads (Dynal Biotech) and then cocultured the binding of HLA class I ligands to four KIR3DL1 allotypes. with irradiated allogeneic PBMCs in RPMI 1640 medium supplemented with 10% heat-inactivated human AB serum (H10) and recombinant human (rh) KIR3DL1 binds to HLA-A*2402 tetramers IL-2 at 100U/ml for 2 wk. NK cell clones were generated by limiting dilution and cultured in H10 with rhIL-2 at 200U/ml and rhIL-15 at 10 ␮g/ml with Four NK clones from three donors either expressed 3DL1*001 irradiated feeder cells.
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