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.

Cloning, localization, and structure of new members of the butyrophilin gene family in the juxta-telomeric region of the major histocompatibility complex.

New members of the butyrophilin (BT) gene family have been identified by cDNA and genomic cloning. Six genes are described: BT2. 1, 2.2, 2.3, and BT3.1, 3.2, and 3.3. BT2, BT3, and BT form three distinct subfamilies sharing about 95% amino acid identity at the intra subfamily level and 50% identity at the interfamily level. All the BT2 and BT3 subfamily members map close to BT in the juxta-telomeric region of the major histocompatibility complex. The BT2 members have the canonical structural organization of BT, i.e., two immunoglobulin domains followed by a transmembrane anchor and a B30.2 intracytoplasmic domain. In the BT3 subfamily, only BT3.3 has the structural organization of BT. The two other genes, BT3.1 and BT3.2, code for putative protein without the B30.2 domain. In the case of BT3.2, this is due to an Alu insertion in the B30.2 coding exon, leading to a new polyadenylation site.