A 7-month-old boy,the only child of second-degree cousins,saw a pediatrician for immunologic evaluation after developing Pneumocystis carinii pneumonia.Serum IgG,IgM,and IgA levels were normal.Blood cell count showed 10,600 leukocytes/mm³ and 80% lymphocytes;90% of the lymphocytes were TCR $\alpha$$\beta$⁺CD4⁺.In vitro lymphocyte-proliferative responses to PHA and anti-CD3 were absent,and the pattern of tyrosine-phosphorylated cytoplasmic proteins after anti-CD3 treatment of the T cells was distinctly abnormal.This boy most likely carries homozygous mutations in the gene encoding which one of the following proteins? A)Zap-70 B)RAG-1 C)CD3 D)Pre-T$\alpha$ E)TCR$\alpha$

Question

Quizplus · Accepted Answer

The patient shows signaling defects in TCR-mediated T cell activation,as well as defects in CD8⁺ T cell maturation.Zap-70 is a tyrosine kinase required for TCR-mediated T cell activation.Mutations in Zap-70 result in impaired TCR signaling,with abnormal tyrosine phosphorylation of downstream signaling molecules,and also a defect in CD8⁺ T cell maturation.It is not known why CD8⁺ maturation is selectively impaired in Zap-70 deficiency.VDJ recombination,and therefore RAG-1 function,must still be intact because TCR-expressing CD4⁺ T cells do mature.CD3,pre-TF1F1F1S1?F1F1F10,and TCRF1F1F1S1?F1F1F10 are also required for maturation of CD4⁺ T cells,and therefore these molecules must all be expressed by this patient.

A 7-Month-Old Boy,the Only Child of Second-Degree Cousins,saw a Pediatrician α\alphaα

A 7-Month-Old Boy,the Only Child of Second-Degree Cousins,saw a Pediatrician $\alpha$