Transfer of putative complementarity-determining region loops of T cell receptor V domains confers toxin reactivity but not peptide/MHC specificity

• Published in: The Journal of immunology (1950) Vol. 150; no. 6; pp. 2281 - 2294
• Main Authors: Patten, PA, Rock, EP, Sonoda, T, Fazekas de St. Groth, B, Jorgensen, JL, Davis, MM
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Assoc Immnol 15.03.1993; American Association of Immunologists
• Subjects: Animals; Base Sequence; Biological and medical sciences; Enterotoxins - chemistry; Enterotoxins - genetics; Epitopes - chemistry; Epitopes - genetics; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Genetic Vectors; Genetics of the immune response; Histocompatibility Antigens Class II - chemistry; Histocompatibility Antigens Class II - genetics; Humans; Immunobiology; Immunoglobulin Variable Region - chemistry; Immunoglobulin Variable Region - genetics; Mice; Molecular Sequence Data; Mutagenesis, Site-Directed; Peptides - chemistry; Peptides - genetics; Peptides - immunology; Protein Conformation; Receptors, Antigen, T-Cell, alpha-beta - chemistry; Receptors, Antigen, T-Cell, alpha-beta - genetics; Receptors, Antigen, T-Cell, alpha-beta - immunology; Structure-Activity Relationship; Transfection; T cell receptor; Peptides; Variable region; Major histocompatibility system; Site directed mutagenesis; Genetic transfer; Immunogenetics; Gene; T-Lymphocyte; Enterotoxin; Bacteria; Micrococcales; Micrococcaceae; Property structure relationship; Recognition; Staphylococcus aureus
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.150.6.2281

We have used multiple-amino acid replacement mutagenesis to examine the roles of the TCR homologues of Ig complementarity-determining regions (CDR) and framework sequences in Ag-MHC and Staphylococcus aureus enterotoxin reactivity. In the three cases examined, transplantation of Ig CDR3 homologues between I-Ek-restricted TCR that recognize distinct peptides did not result in transfer of peptide reactivity. Thus the structural context of the CDR3 loops, e.g., both neighboring CDR and the V beta structure, must play a crucial, albeit supporting, role in ligand recognition. The extreme lability of this context was also shown by the fact that transplantation of the CDR1, -2, and -3 loops from the beta chain of 5C.C7 onto a V beta 1 framework failed to transfer MHC-peptide specificity even when the TCR-alpha chains were identical. In contrast, superantigen reactivity was readily transferred in several cases, with CDR2 transplants conferring strong staphylococcal enterotoxin B and A reactivity and CDR1 transplants yielding weak reactivities. This suggests that bacterial (and perhaps other) superantigens bind to many of the same regions of the TCR V beta that are believed to interact with MHC molecules. These regions of V beta may be ideal targets for superantigen binding precisely because they interact with MHC molecules and thus may be relatively conserved.