On the genetic mechanism of induction of CD3gamma-negative human T cell variants.
Invariant CD3gamma molecules are important components in TCR complex formation and function. Both CD3gamma alleles seem to be expressed co-dominantly. In the present report, we present experimental data which indicate that the induction of CD3gamma(-) Jurkat variants occurs with a frequency similar to that of TCRalpha(-) or TCRbeta(-) Jurkat cells. CD3delta(-), CD3epsilon(-) or CD3zeta(-) Jurkat variants were never obtained despite extensive efforts. Our data suggest a possible explanation for this genetic puzzle: the human CD3gamma gene has a mutational hot spot in a nucleotide sequence of nine adenosines (9A) in the exon 3 encoding most of the external CD3gamma domain. Thus, both CD3gamma alleles are easily mutated to either 8A or 10A sequences. Furthermore, absence of CD3gamma molecules in Jurkat T cells causes severe defects in TCR / CD3 assembly and function.
Huchenq-Champagne
A
A
Laboratoire d'Immunologie Cellulaire et Moléculaire, CNRS ERS 1590, IFR30 / FR23, Unité de Physiopathologie Cellulaire et Moleculaire, Toulouse, France.
Arnaud
J
J
Bouchouata
C
C
Gouaillard
C
C
Llobera
R
R
Rubin
B
B
D002454:Cell Differentiation / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D019169:Jurkat Cells; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000235:genetics* / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics* / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D017260:Receptor-CD3 Complex, Antigen, T-Cell; D016692:Receptors, Antigen, T-Cell, gamma-delta