The cytoplasmic tail of the T cell receptor CD3 epsilon subunit contains a phospholipid-binding motif that regulates T cell functions.
The CD3 epsilon subunit of the TCR complex contains two defined signaling domains, a proline-rich sequence and an ITAM. We identified a third signaling sequence in CD3 epsilon, termed the basic-rich stretch (BRS). Herein, we show that the positively charged residues of the BRS enable this region of CD3 epsilon to complex a subset of acidic phospholipids, including PI(3)P, PI(4)P, PI(5)P, PI(3,4,5)P(3), and PI(4,5)P(2). Transgenic mice containing mutations of the BRS exhibited varying developmental defects, ranging from reduced thymic cellularity to a complete block in T cell development. Peripheral T cells from BRS-modified mice also exhibited several defects, including decreased TCR surface expression, reduced TCR-mediated signaling responses to agonist peptide-loaded APCs, and delayed CD3 epsilon localization to the immunological synapse. Overall, these findings demonstrate a functional role for the CD3 epsilon lipid-binding domain in T cell biology.
Deford-Watts
Laura M
LM
Department of Immunology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Tassin
Tara C
TC
Becker
Amy M
AM
Medeiros
Jennifer J
JJ
Albanesi
Joseph P
JP
Love
Paul E
PE
Wülfing
Christoph
C
van Oers
Nicolai S C
NS
D020816:Amino Acid Motifs; D024361:Amino Acids, Basic; D000818:Animals; D001665:Binding Sites; D017252:CD3 Complex / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D002460:Cell Line; D003593:Cytoplasm / Q000737:chemistry; D018076:DNA, Complementary; D006801:Humans; D051379:Mice; D009154:Mutation; D010743:Phospholipids / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology
D024361:Amino Acids, Basic; D017252:CD3 Complex; C485468:Cd3e protein, mouse; D018076:DNA, Complementary; D010743:Phospholipids; D011948:Receptors, Antigen, T-Cell