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Allelic polymorphism synergizes with variable gene content to individualize human KIR genotype
Heather G Shilling1, Lisbeth A Guethlein, Nathalie W Cheng
1Department of Structural Biology and Microbiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|February 23, 2002
Summary
Killer-cell immunoglobulin-like receptor (KIR) gene polymorphism creates unique genotypes. This diversity in KIR haplotypes, driven by allelic variations and gene content, likely enhances the human immune response to pathogens.
Area of Science:
- Immunogenetics
- Human genetics
- Molecular immunology
Background:
- Killer-cell immunoglobulin-like receptor (KIR) genes form a multigene family on human chromosome 19.
- KIR genes exhibit significant allelic polymorphism and occur in diverse combinations on different haplotypes.
- Understanding KIR haplotype diversity is crucial for immune response studies.
Purpose of the Study:
- To investigate how allelic polymorphism diversifies Killer-cell immunoglobulin-like receptor (KIR) haplotypes.
- To develop and apply methods for discriminating specific KIR gene alleles.
- To define KIR haplotypes at the allele level and analyze their combinations.
Main Methods:
- Devised methods to discriminate alleles of KIR2DL1, KIR2DL3, KIR3DL1, and KIR3DL2.
- Applied these methods to 143 individuals from 34 families.
- Defined 98 independent KIR haplotypes at the allele level.
Main Results:
- Identified 98 independent KIR haplotypes at the allele level, including novel alleles and a chimeric sequence.
- Characterized 22 distinct allele combinations within A group haplotypes and 15 within B group haplotypes.
- Observed strong linkage disequilibrium (LD) between specific allele pairs within KIR haplotypes, but limited LD between the two halves of the KIR gene complex.
Conclusions:
- The combination of allelic polymorphism and variable gene content results in highly individualized KIR genotypes.
- Unrelated individuals typically possess distinct KIR types, highlighting extensive genetic diversity.
- This high level of KIR diversity is likely a result of evolutionary pressure from pathogens on the human natural killer (NK) cell response.