Identification of Tapr (An Airway Hyperreactivity Regulatory Locus) and the Linked Tim Gene Family

Nat Immunol. 2001 Dec;2(12):1109-16. doi: 10.1038/ni739.


To simplify the analysis of asthma susceptibility genes located at human chromosome 5q23-35, we examined congenic mice that differed at the homologous chromosomal segment. We identified a Mendelian trait encoded by T cell and Airway Phenotype Regulator (Tapr). Tapr is genetically distinct from known cytokine genes and controls the development of airway hyperreactivity and T cell production of interleukin 4 (IL-4) and IL-13. Positional cloning identified a gene family that encodes T cell membrane proteins (TIMs); major sequence variants of this gene family (Tim) completely cosegregated with Tapr. The human homolog of TIM-1 is the hepatitis A virus (HAV) receptor, which may explain the inverse relationship between HAV infection and the development of atopy.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Asthma / genetics*
  • Asthma / immunology
  • Bronchial Hyperreactivity / genetics*
  • Bronchial Hyperreactivity / immunology
  • Cells, Cultured
  • Chromosome Mapping
  • Chromosomes, Human, Pair 5
  • Cloning, Molecular
  • Genetic Predisposition to Disease
  • Hepatitis A Virus Cellular Receptor 1
  • Hepatitis A Virus Cellular Receptor 2
  • Humans
  • Interleukin-13 / biosynthesis
  • Interleukin-4 / biosynthesis
  • Membrane Glycoproteins / genetics
  • Membrane Proteins / genetics*
  • Membrane Proteins / physiology
  • Mice
  • Mice, Inbred DBA
  • Molecular Sequence Data
  • Multigene Family
  • Polymorphism, Genetic
  • Receptors, Virus / genetics
  • Sequence Homology, Amino Acid
  • T-Lymphocytes, Helper-Inducer / immunology*


  • HAVCR1 protein, human
  • Havcr1 protein, mouse
  • Havcr2 protein, mouse
  • Hepatitis A Virus Cellular Receptor 1
  • Hepatitis A Virus Cellular Receptor 2
  • Interleukin-13
  • Membrane Glycoproteins
  • Membrane Proteins
  • Receptors, Virus
  • Timd2 protein, mouse
  • Interleukin-4

Associated data

  • GENBANK/AF399827
  • GENBANK/AF399828
  • GENBANK/AF399829
  • GENBANK/AF399830
  • GENBANK/AF399831