Anti-CD3D monoclonal antibody, clone D474.30C [FITC]

Polymorphism of the genes encoding the alpha, beta, and gamma chains of the human T-cell receptor (TCRA, TCRB, and TCRG), insulin gene (INS), and three closely linked polymorphic genes on chromosome 11q23, Thy-1 (THY1), T3-D (CD3D), and c-ets proto oncogene (ETSl) were investigated among 56 unrelated patients with insulin-dependent diabetes mellitus (IDDM) and 48 healthy controls. Only eight of the 17 enzymes examined revealed restriction fragment length polymorphism (RFLP), with the use of TCRA, TCRB, and TCRG. No significant association was observed. Polymorphism after BglI, SstI, and TaqI digestion was observed for the INS gene. In consideration of the three classes within the insulin-gene-linked DNA polymorphism alleles, Al and more rarely A2 alleles were found, but with no significant frequencies. THYl and CD3D genes were polymorphic after MspI digestion but no significant association was observed. Conversely, the ETSl gene showed polymorphism after TaqI, SstI, and AvaII were used. Only a significant AvaII-polymorphic fragment (p < 0.03) was found. However, this significant association disappeared when the corrected p value was applied. These results were compared to findings in Caucasians and some differences were noted. The polymorphism observed in this study may be useful in genetic studies on immunologically affected populations.

T cells recognize antigens via their cell surface TCR and are classified as either alpha beta or gamma delta depending on the variable chains in their TCR, alpha and beta or gamma and delta, respectively. Both alpha beta and gamma delta TCRs also contain several invariant chains, including CD3 delta, which support surface TCR expression and transduce the TCR signal. Mutations in variable chains would be expected to affect a single T cell lineage, while mutations in the invariant chains would affect all T cells. Consistent with this, all CD3 delta-deficient patients described to date showed a complete block in T cell development. However, CD3 delta-KO mice have an alpha beta T cell-specific defect. Here, we report 2 unrelated cases of SCID with a selective block in alpha beta but not in gamma delta T cell development, associated with a new splicing mutation in the CD3D gene. The patients' T cells showed reduced CD3D transcripts, CD3 delta proteins, surface TCR, and early TCR signaling. Their lymph nodes showed severe T cell depletion, recent thymus emigrants in peripheral blood were strongly decreased, and the scant alpha beta T cells were oligoclonal. T cell-dependent B cell functions were also impaired, despite the presence of normal B cell numbers. Strikingly, despite the specific loss of alpha beta T cells, surface TCR expression was more reduced in gamma delta than in alpha beta T cells. Analysis of individuals with this CD3D mutation thus demonstrates the contrasting CD3 delta requirements for alpha beta versus gamma delta T cell development and TCR expression in humans and highlights the diagnostic and clinical relevance of studying both TCR isotypes when a T cell defect is suspected.