HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sanjanwala, B. Articles by Parham, P. Search for Related Content PubMed PubMed Citation Articles by Sanjanwala, B. Articles by Parham, P.

Polymorphic Sites Away from the Bw4 Epitope That Affect Interaction of Bw4⁺ HLA-B with KIR3DL1¹

Department of Structural Biology, Stanford University, Stanford, CA 94305

KIR3DL1 is a polymorphic, inhibitory NK cell receptor specific for the Bw4 epitope carried by subsets of HLA-A and HLA-B allotypes. The Bw4 epitope of HLA-B*5101 and HLA-B*1513 is determined by the NIALR sequence motif at positions 77, 80, 81, 82, and 83 in the ₁ helix. Mutation of these positions to the residues present in the alternative and nonfunctional Bw6 motif showed that the functional activity of the Bw4 epitopes of B*5101 and B*1513 is retained after substitution at positions 77, 80, and 81, but lost after substitution of position 83. Mutation of leucine to arginine at position 82 led to loss of function for B*5101 but not for B*1513. Further mutagenesis, in which B*1513 residues were replaced by their B*5101 counterparts, showed that polymorphisms in all three extracellular domains contribute to this functional difference. Prominent were positions 67 in the ₁ domain, 116 in the ₂ domain, and 194 in the ₃ domain. Lesser contributions were made by additional positions in the ₂ domain. These positions are not part of the Bw4 epitope and include residues shaping the B and F pockets that determine the sequence and conformation of the peptides bound by HLA class I molecules. This analysis shows how polymorphism at sites throughout the HLA class I molecule can influence the interaction of the Bw4 epitope with KIR3DL1. This influence is likely mediated by changes in the peptides bound, which alter the conformation of the Bw4 epitope.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grants AI064520 and AI022309.

² Current address: Department of Pediatrics, Stanford University; Stanford, CA 94305.

³ Current address: Department of Pediatrics, Division of Immunology and Transplantation Biology, Stanford University School of Medicine, Stanford, CA 94305.

⁴ Address correspondence and reprint requests to Dr. Peter Parham or Dr. Lisbeth A. Guethlein, Department of Structural Biology, Stanford University, Fairchild D-157, 299 Campus Drive West, Stanford, CA 94305-5126. E-mail addresses: peropa{at}stanford.edu and lisbeth.guethlein{at}stanford.edu

⁵ Abbreviation used in this paper: KIR, killer cell Ig-like receptors.

This article has been cited by other articles:

				M. Morvan, C. Willem, K. Gagne, N. Kerdudou, G. David, V. Sebille, G. Follea, J.-D. Bignon, and C. Retiere Phenotypic and Functional Analyses of KIR3DL1+ and KIR3DS1+ NK Cell Subsets Demonstrate Differential Regulation by Bw4 Molecules and Induced KIR3DS1 Expression on Stimulated NK Cells J. Immunol., June 1, 2009; 182(11): 6727 - 6735. [Abstract] [Full Text] [PDF]