On the genetic mechanism of induction of CD3γ-negative human T cell variants

Abstract

Invariant CD3γ molecules are important components in TCR complex formation and function. Both CD3γ alleles seem to be expressed co-dominantly. In the present report, we present experimental data which indicate that the induction of CD3γ– Jurkat variants occurs with a frequency similar to that of TCRα– or TCRβ– Jurkat cells. CD3δ–, CD3ϵ– or CD3ζ– Jurkat variants were never obtained despite extensive efforts. Our data suggest a possible explanation for this genetic puzzle: the human CD3γ gene has a mutational hot spot in a nucleotide sequence of nine adenosines (9A) in the exon 3 encoding most of the external CD3γ domain. Thus, both CD3γ alleles are easily mutated to either 8A or 10A sequences. Furthermore, absence of CD3γ molecules in Jurkat T cells causes severe defects in TCR / CD3 assembly and function.