© The Rockefeller University Press, 0022-1007/1999/7/31/ $5.00
The Journal of Experimental Medicine, Volume 190, Number 1, July 1, 1999 31-42
Dependence of T Cell Antigen Recognition on the Dimensions of an Accessory Receptor–Ligand Complex
Martin K. Wilda,
Anna Cambiaggia,
Marion H. Browna,
Elizabeth A. Daviesa,
Hiroshi Ohnob,
Takashi Saitoc, and
P. Anton van der Merwea
a From the Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom
b Division of Molecular Membrane Biology, Cancer Research Institute, Kanazawa University, Kanazawa 920-0934, Japan
c Department of Molecular Genetics, Chiba University Graduate School of Medicine, Chuo-ku, Chiba 260-8670, Japan
The T cell antigen receptor (TCR) and its ligand peptide–major histocompatibility complex (MHC) are small (
7 nm) compared with other abundant cell surface molecules such as integrins, CD43, and CD45 (23–50 nm). We have proposed that molecules at the T cell/antigen-presenting cell (APC) interface segregate according to size, with small "accessory" molecules (e.g., CD2, CD4, CD8, CD28, and CD154) contributing to the formation of a close-contact zone, within which the TCR engages peptide–MHC, and from which large molecules are excluded (Davis, S.J., and P.A. van der Merwe. 1996. Immunol. Today. 17:177–187). One prediction of this model is that increasing the size of these small accessory molecules will disrupt their function. Here, we test this prediction by varying the dimensions of the CD2 ligand, CD48, and examining how this affects T cell antigen recognition. Although the interaction of CD2 on T cells with wild-type or shortened forms of CD48 on APCs enhances T cell antigen recognition, the interaction of CD2 with elongated forms of CD48 is strongly inhibitory. Further experiments indicated that elongation of the CD2/CD48 complex inhibited TCR engagement of peptide–MHC, presumably by preventing the formation of sufficiently intimate contacts at the T cell/APC interface. These findings demonstrate the importance of small size in CD2/CD48 function, and support the hypothesis that T cell antigen recognition requires segregation of cell surface molecules according to size.
Key Words: T cell receptor CD2 CD48 T cell activation plasma membrane
1used in this paper: CHO, Chinese hamster ovary; GPI, glycosyl phosphatidylinositol; ICAM, intercellular adhesion molecule; MCC, moth cytochrome c
© 1999 The Rockefeller University Press

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