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Howard Hughes Medical Institute, The Rockefeller University, New York 10021; the
Howard Hughes Medical Institute, Ruttenberg Cancer Center, Mount Sinai School of Medicine, New York 10029; and the || Immunology Program, Graduate School of Medical Sciences, and the Department of Medicine, Cornell University Medical College, New York 10021
Superantigens are defined as proteins that activate a large number of T cells through interaction with the Vβ region of the T cell antigen receptor (TCR). Here we demonstrate that the superantigen produced by Mycoplasma arthritidis (MAM), unlike six bacterial superantigens tested, interacts not only with the Vβ region but also with the CDR3 (third complementarity-determining region) of TCR-β. Although MAM shares typical features with other superantigens, direct interaction with CDR3-β is a feature of nominal peptide antigens situated in the antigen groove of major histocompatibility complex (MHC) molecules rather than superantigens. During peptide recognition, Vβ and V
domains of the TCR form contacts with MHC and the complex is stabilized by CDR3–peptide interactions. Similarly, recognition of MAM is Vβ-dependent and is apparently stabilized by direct contacts with the CDR3-β region. Thus, MAM represents a new type of ligand for TCR, distinct from both conventional peptide antigens and other known superantigens.
1 Abbreviations used in this paper: MAM, Mycoplasma arthritidis mitogen; MMTV, mouse mammary tumor virus; SE, staphylococcal enterotoxin.
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