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T-B+NK+ severe combined immunodeficiency caused by complete deficiency of the CD3zeta subunit of the T-cell antigen receptor complex.

Publication ,  Journal Article
Roberts, JL; Lauritsen, JPH; Cooney, M; Parrott, RE; Sajaroff, EO; Win, CM; Keller, MD; Carpenter, JH; Carabana, J; Krangel, MS; Sarzotti, M ...
Published in: Blood
April 15, 2007

CD3zeta is a subunit of the T-cell antigen receptor (TCR) complex required for its assembly and surface expression that also plays an important role in TCR-mediated signal transduction. We report here a patient with T(-)B(+)NK(+) severe combined immunodeficiency (SCID) who was homozygous for a single C insertion following nucleotide 411 in exon 7 of the CD3zeta gene. The few T cells present contained no detectable CD3zeta protein, expressed low levels of cell surface CD3epsilon, and were nonfunctional. CD4(+)CD8(-)CD3epsilon(low), CD4(-)CD8(+)CD3epsilon(low), and CD4(-)CD8(-)CD3epsilon(low) cells were detected in the periphery, and the patient also exhibited an unusual population of CD56(-)CD16(+) NK cells with diminished cytolytic activity. Additional studies demonstrated that retrovirally transduced patient mutant CD3zeta cDNA failed to rescue assembly of nascent complete TCR complexes or surface TCR expression in CD3zeta-deficient MA5.8 murine T-cell hybridoma cells. Nascent transduced mutant CD3zeta protein was also not detected in metabolically labeled MA5.8 cells, suggesting that it was unstable and rapidly degraded. Taken together, these findings provide the first demonstration that complete CD3zeta deficiency in humans can cause SCID by preventing normal TCR assembly and surface expression.

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Published In

Blood

DOI

ISSN

0006-4971

Publication Date

April 15, 2007

Volume

109

Issue

8

Start / End Page

3198 / 3206

Location

United States

Related Subject Headings

  • Transduction, Genetic
  • T-Lymphocytes
  • Severe Combined Immunodeficiency
  • Retroviridae
  • Receptors, Antigen, T-Cell
  • Mutagenesis, Insertional
  • Multiprotein Complexes
  • Killer Cells, Natural
  • Infant
  • Immunology
 

Citation

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MLA
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Roberts, J. L., Lauritsen, J. P. H., Cooney, M., Parrott, R. E., Sajaroff, E. O., Win, C. M., … Buckley, R. H. (2007). T-B+NK+ severe combined immunodeficiency caused by complete deficiency of the CD3zeta subunit of the T-cell antigen receptor complex. Blood, 109(8), 3198–3206. https://doi.org/10.1182/blood-2006-08-043166
Roberts, Joseph L., Jens Peter H. Lauritsen, Myriah Cooney, Roberta E. Parrott, Elisa O. Sajaroff, Chan M. Win, Michael D. Keller, et al. “T-B+NK+ severe combined immunodeficiency caused by complete deficiency of the CD3zeta subunit of the T-cell antigen receptor complex.Blood 109, no. 8 (April 15, 2007): 3198–3206. https://doi.org/10.1182/blood-2006-08-043166.
Roberts JL, Lauritsen JPH, Cooney M, Parrott RE, Sajaroff EO, Win CM, et al. T-B+NK+ severe combined immunodeficiency caused by complete deficiency of the CD3zeta subunit of the T-cell antigen receptor complex. Blood. 2007 Apr 15;109(8):3198–206.
Roberts, Joseph L., et al. “T-B+NK+ severe combined immunodeficiency caused by complete deficiency of the CD3zeta subunit of the T-cell antigen receptor complex.Blood, vol. 109, no. 8, Apr. 2007, pp. 3198–206. Pubmed, doi:10.1182/blood-2006-08-043166.
Roberts JL, Lauritsen JPH, Cooney M, Parrott RE, Sajaroff EO, Win CM, Keller MD, Carpenter JH, Carabana J, Krangel MS, Sarzotti M, Zhong X-P, Wiest DL, Buckley RH. T-B+NK+ severe combined immunodeficiency caused by complete deficiency of the CD3zeta subunit of the T-cell antigen receptor complex. Blood. 2007 Apr 15;109(8):3198–3206.

Published In

Blood

DOI

ISSN

0006-4971

Publication Date

April 15, 2007

Volume

109

Issue

8

Start / End Page

3198 / 3206

Location

United States

Related Subject Headings

  • Transduction, Genetic
  • T-Lymphocytes
  • Severe Combined Immunodeficiency
  • Retroviridae
  • Receptors, Antigen, T-Cell
  • Mutagenesis, Insertional
  • Multiprotein Complexes
  • Killer Cells, Natural
  • Infant
  • Immunology