The high affinity Fc epsilon receptor gamma subunit (Fc epsilon RI gamma) facilitates T cell receptor expression and antigen/major histocompatibility complex-driven signaling in the absence of CD3 zeta and CD3 eta.
The T cell receptor (TCR) is a molecular complex formed by at least seven transmembrane proteins: the antigen/major histocompatibility complex recognition unit (Ti alpha-beta heterodimer) and the invariant CD3 chains (gamma, delta, epsilon, zeta, and eta). In addition to targeting partially assembled Ti alpha-beta CD3 gamma delta epsilon TCR complexes to the cell surface, CD3 zeta appears to be essential for interleukin-2 production after TCR stimulation with antigen/major histocompatibility complex. The gamma chain of the high affinity Fc receptor for IgE (Fc epsilon RI gamma) has significant structural homology to CD3 zeta and the related CD3 eta subunit. To identify the functional significance of sequence homologies between CD3 zeta and Fc epsilon RI gamma in T cells, we have transfected a Fc epsilon RI gamma cDNA into a T cell hybridoma lacking CD3 zeta and CD3 eta proteins. Herein we show that a Fc epsilon RI gamma-gamma homodimer associates with TCR components to up-regulate TCR surface expression. A TCR composed of Ti alpha-beta CD3 gamma delta epsilon Fc epsilon RI gamma-gamma is sufficient to restore the coupling of TCR antigen recognition to the interleukin-2 induction pathway, demonstrating the functional significance of structural homology between the above receptor subunits. These results, in conjunction with the recent finding that CD3 zeta, CD3 eta, and Fc epsilon RI gamma are coexpressed in certain T cells as subunits of an unusual TCR isoform, suggest that Fc epsilon RI gamma is likely to play a role in T cell lineage function.
Rodewald
H R
HR
Laboratory of Immunobiology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Arulanandam
A R
AR
Koyasu
S
S
Reinherz
E L
EL
D000595:Amino Acid Sequence; D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D015152:Blotting, Northern; D015153:Blotting, Western; D017252:CD3 Complex; D004247:DNA / Q000235:genetics; D005786:Gene Expression Regulation; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D008285:Major Histocompatibility Complex; D008969:Molecular Sequence Data; D011233:Precipitin Tests; D012313:RNA / Q000032:analysis; D051381:Rats; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis* / Q000276:immunology* / Q000378:metabolism; D011961:Receptors, Fc / Q000378:metabolism*; D017455:Receptors, IgE; D016415:Sequence Alignment; D015398:Signal Transduction; D013379:Substrate Specificity; D014162:Transfection
D000944:Antigens, Differentiation, B-Lymphocyte; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D011961:Receptors, Fc; D017455:Receptors, IgE; D012313:RNA; D004247:DNA