Mycoplasma superantigen is a CDR3-dependent ligand for the T cell antigen receptor

Superantigens are defined as proteins that activate a large number of T cells through interaction with the V beta region of the T cell antigen receptor (TCR). Here we demonstrate that the superantigen produced by Mycoplasma ai arthritidis (MAM), unlike six bacterial superantigens tested, interacts not only with the V beta region but also with the CDR3 (third complementarity-determining region) of TCR-beta. Although MAN shares typical features with other superantigens, direct interaction with CDR3-beta is a feature of nominal peptide antigens situated in the antigen groove of major histocompatibility complex (MHC) molecules rather than superantigens. During peptide recognition, V beta and V alpha. domains of the TCR form contacts with MHC and the V beta-dependent and is apparently stabilized by direct contacts with the CDR3-beta region. Thus, MAM represents a new type of ligand for TCR, distinct from both conventional peptide antigens and other known superantigens.