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Activation-induced Modification in the CD3 Complex of the T Cell Receptor

Sandra M. Hayes¹, Karen Laky², Dalal El-Khoury¹, Dietmar J. Kappes³, B.J. Fowlkes² and Paul E. Love¹

¹ Laboratory of Mammalian Genes and Development, National Institute of Child Health and Human Development
² Laboratory of Molecular and Cellular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
³ Division of Basic Science, Fox Chase Cancer Center, Philadelphia, PA 19111

Address correspondence to Paul E. Love, Laboratory of Mammalian Genes and Development, NICHD/NIH Bldg. 6B, Rm. 2B-210, 9000 Rockville Pike, Bethesda, MD 20892-2780. Phone: 301-402-4946; Fax: 301-480-6302; E-mail: pel{at}helix.nih.gov

The T cell antigen receptor complexes expressed on ß and T cells differ not only in their respective clonotypic heterodimers but also in the subunit composition of their CD3 complexes. The T cell receptors (TCRs) expressed on ex vivo T cells lack CD3, whereas ß TCRs contain CD3. While this result correlates with the phenotype of CD3^-/- mice, in which T cell development is unaffected, it is inconsistent with the results of previous studies reporting that CD3 is a component of the TCR. Since earlier studies examined the subunit composition of TCRs expressed on activated and expanded peripheral T cells or TCR⁺ intestinal intraepithelial lymphocytes, we hypothesized that activation and expansion may lead to changes in the CD3 subunit composition of the TCR. Here, we report that activation and expansion do in fact result in the inclusion of a protein, comparable in mass and mobility to CD3, in the TCR. Further analyses revealed that this protein is not CD3, but instead is a differentially glycosylated form of CD3. These results provide further evidence for a major difference in the subunit composition of ß- and TCR complexes and raise the possibility that modification of CD3 may have important functional consequences in activated T cells.

Key Words: T cell receptor • structure • glycosylation • CD3 • activation

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