Dependence of T cell antigen recognition on the dimensions of an accessoryreceptor-ligand complex

The T cell antigen receptor (TCR) and its ligand peptide-major histocompati bility complex (MHC) are small (similar to 7 nm) compared with other abunda nt 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) in terface 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 larg e molecules are es eluded (Davis, S.J. and P.A. van der Merwe. 1996. Immuno l. 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 int eraction of CD2 on T cells with wild-type or shortened forms of CD48 on APC s enhances T cell antigen recognition the interaction of CD2 with elongated forms of CD48 is strongly inhibitory. Further experiments indicated that e longation 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 sma ll size in CD2/CD48 function, and support the hypothesis that T cell antige n recognition requires segregation of cell surface molecules according to s ize.