Consequences of a mutation in the UNC119 gene for T cell function in idiopathic CD4 lymphopenia.
The activation of a T cell through T cell receptor (TCR) is fundamental to adaptive immune responses. The lymphocyte specific kinase (LCK) plays a central role in the initiation of signaling from the TCR. TCR activates LCK through the adaptor protein uncoordinated 119 (UNC119). A mutation of human UNC119 impairs LCK activation and is associated with inadequate signaling, diminished T cell responses to TCR stimulation, CD4 lymphopenia, and infections of viral, bacterial, and fungal origin. The above clinical and immunological findings meet the criteria of the idiopathic CD4 lymphopenia (ICL). The discovery of the UNC119 defect provides a molecular mechanism for a subset of patients with this previously unexplained disease. Here we review our recent findings on the UNC119 mutation in ICL.
Department of Medicine, Division of Allergy and Immunology, National Jewish Health, 1400 Jackson St, Denver, CO 80206, USA. gorskam@njhealth.org
Magdalena M
MM
Gorska
Rafeul
R
Alam
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D017668:Age of Onset; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004789:Enzyme Activation / Q000235:genetics / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000378:metabolism*; D008231:Lymphopenia / Q000235:genetics* / Q000276:immunology*; D020125:Mutation, Missense; D058499:Retinal Dystrophies / Q000235:genetics / Q000276:immunology; D016511:Severe Combined Immunodeficiency / Q000235:genetics / Q000276:immunology
D048868:Adaptor Proteins, Signal Transducing; C098032:UNC119 protein, human; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)