Conserved amino acid residues in the complementarity-determining region 1 of the TCR beta-chain are involved in the recognition of conventional Ag and Mls-1 superantigen.
Superantigens activate T cells by interacting primarily with the V beta region of the TCR. This report describes a series of studies performed to elucidate the role of the conserved amino acid motif (Asp-His-Asn) in the complementarity-determining region 1 (CDR1) of the TCR V beta chains that recognize murine endogenous superantigen Mls-1. By using site-directed mutagenesis of the Mls-1-reactive TCR V beta 6 gene, it is shown that the alterations of the conserved CDR1 motif disrupt Mls-1 superantigen and conventional Ag recognition in vitro. The loss of V beta 6 (mutant)+ TCR reactivity to Mls-1 superantigen is apparently dependent on the partner alpha-chain in the V beta 6/V alpha 3 TCR pairing shows some reactivity to Mls-1, whereas other TCR pairings do not. The examination of the developmental fate of the mutated form of the V beta 6 chain in Mls-1+ mice by using retroviral vector-mediated gene transfer confirms the critical role played by the CDR1 residues in Mls-1 recognition in vivo. Collectively, the results indicate that the CDR1 of the TCR V beta 6 chain is involved in interacting with peptide/MHC as well as in Mls-1 recognition. The observation that the conserved residues in selective TCR V beta chains are imparting a significant contribution to Ag recognition suggests a molecular basis for the intrinsic bias of some V beta chains for MHC molecules.
Kang
J
J
Division of Molecular Immunology and Neurobiology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada.
Chambers
C A
CA
Pawling
J
J
Scott
C
C
Hozumi
N
N
D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens / Q000276:immunology*; D015704:CD4 Antigens / Q000032:analysis; D002460:Cell Line; D017124:Conserved Sequence; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D016747:Minor Lymphocyte Stimulatory Antigens / Q000276:immunology*; D008969:Molecular Sequence Data; D009154:Mutation; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology
D000941:Antigens; D015704:CD4 Antigens; D016747:Minor Lymphocyte Stimulatory Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta