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The D0 domain of KIR3D acts as a major histocompatibility complex class I binding enhancer

The D0 domain of KIR3D acts as a major histocompatibility complex class I binding enhancer
The D0 domain of KIR3D acts as a major histocompatibility complex class I binding enhancer
In contrast to the KIR2D:HLA-C interaction, little is known of KIR3DL1's interaction with HLA-B or the role of D0, the domain not present in KIR2D. Differences in the strength and specificity for major histocompatibility complex class I of KIR3DL1 and its common chimpanzee homologue Pt-KIR3DL1/2 were exploited to address these questions. Domain-swap, deletion, and site-directed mutants of KIR3DL1 were analyzed for HLA-B binding using a novel, positively signaling cell-cell binding assay. Natural 'deletion' of residues 50 and 51 from its D0 domain causes Pt-KIR3DL1/2 to bind Bw4(+) HLA-B allotypes more avidly than does KIR3DL1. Deletion of these residues from KIR3DL1, or their substitution for alanine, enhanced binding of Bw4(+) HLA-B. None of 15 different point mutations in D0 abrogated KIR3DL1 binding to Bw4(+) HLA-B. In contrast point mutations in the D1 and D2 domains of KIR3DL1, made from knowledge of KIR2D:HLA-C interactions, disrupted binding to Bw4(+) HLA-B. The results are consistent with a model in which D1 and D2 make the principal contacts between KIR3DL1 and HLA-B while D0 acts through a different mechanism to enhance the interaction. This modulatory role for D0 is compatible with natural loss of expression of the D0 domain, a repeated event in the evolution of functional KIR genes.
natural killer cells, killer cell immunoglobulin-like receptors, MHC class I, human, chimpanzee
0022-1007
911-921
Khakoo, Salim I.
6c16d2f5-ae80-4d9b-9100-6bfb34ad0273
Geller, Ron
e963a7a9-f9cf-41aa-90eb-dd9dde102162
Shin, Sunny
a69b89dd-92ad-4aec-bafa-9bfcba10e063
Jenkins, Jomaquai A.
596b0d90-e1eb-4b0b-8a58-52194a454b97
Parham, Peter
85caaa6b-edd8-4239-b69b-b24043d52f9e
Khakoo, Salim I.
6c16d2f5-ae80-4d9b-9100-6bfb34ad0273
Geller, Ron
e963a7a9-f9cf-41aa-90eb-dd9dde102162
Shin, Sunny
a69b89dd-92ad-4aec-bafa-9bfcba10e063
Jenkins, Jomaquai A.
596b0d90-e1eb-4b0b-8a58-52194a454b97
Parham, Peter
85caaa6b-edd8-4239-b69b-b24043d52f9e

Khakoo, Salim I., Geller, Ron, Shin, Sunny, Jenkins, Jomaquai A. and Parham, Peter (2002) The D0 domain of KIR3D acts as a major histocompatibility complex class I binding enhancer. The Journal of Experimental Medicine, 196 (7), 911-921. (doi:10.1084/jem.20020304).

Record type: Article

Abstract

In contrast to the KIR2D:HLA-C interaction, little is known of KIR3DL1's interaction with HLA-B or the role of D0, the domain not present in KIR2D. Differences in the strength and specificity for major histocompatibility complex class I of KIR3DL1 and its common chimpanzee homologue Pt-KIR3DL1/2 were exploited to address these questions. Domain-swap, deletion, and site-directed mutants of KIR3DL1 were analyzed for HLA-B binding using a novel, positively signaling cell-cell binding assay. Natural 'deletion' of residues 50 and 51 from its D0 domain causes Pt-KIR3DL1/2 to bind Bw4(+) HLA-B allotypes more avidly than does KIR3DL1. Deletion of these residues from KIR3DL1, or their substitution for alanine, enhanced binding of Bw4(+) HLA-B. None of 15 different point mutations in D0 abrogated KIR3DL1 binding to Bw4(+) HLA-B. In contrast point mutations in the D1 and D2 domains of KIR3DL1, made from knowledge of KIR2D:HLA-C interactions, disrupted binding to Bw4(+) HLA-B. The results are consistent with a model in which D1 and D2 make the principal contacts between KIR3DL1 and HLA-B while D0 acts through a different mechanism to enhance the interaction. This modulatory role for D0 is compatible with natural loss of expression of the D0 domain, a repeated event in the evolution of functional KIR genes.

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More information

Published date: 2002
Keywords: natural killer cells, killer cell immunoglobulin-like receptors, MHC class I, human, chimpanzee

Identifiers

Local EPrints ID: 27199
URI: http://eprints.soton.ac.uk/id/eprint/27199
ISSN: 0022-1007
PURE UUID: 4618cfa4-97cf-4696-8d03-0fc97874dc79

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Date deposited: 27 Apr 2006
Last modified: 15 Jul 2019 19:12

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