Department of Microbiology Papers
Document Type
Journal Article
Date of this Version
10-7-2002
Publication Source
Journal of Experimental Medicine
Volume
196
Issue
7
Start Page
911
Last Page
921
DOI
10.1084/jem.20020304
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.
Copyright/Permission Statement
© Salim I. Khakoo, Ron Geller, Sunny Shin, Jomaquai A. Jenkins, Peter Parham, 2002. Originally published in Journal of Experimental Medicine. doi: 10.1084/jem.20020304.
Recommended Citation
Khakoo, Salim I.; Geller, Ron; Shin, Sunny; Jenkins, Jomaquai A.; and Parham, Peter, "The D0 Domain of KIR3D Acts as a Major Histocompatibility Complex Class I Binding Enhancer" (2002). Department of Microbiology Papers. 1.
https://repository.upenn.edu/microbiology/1
Date Posted: 17 June 2015
This document has been peer reviewed.
Comments
At the time of publication, author Sunny Shin was affiliated with Standford University School of Medicine. Currently, she is a faculty member at the Perelman School of Medicine at the University of Pennsylvania.