Transfer of putative complementarity-determining region loops of T cell receptor V domains confers toxin reactivity but not peptide/MHC specificity
| Autor: | P A, Patten, E P, Rock, T, Sonoda, B, Fazekas de St Groth, J L, Jorgensen, M M, Davis |
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| Rok vydání: | 1993 |
| Předmět: |
Base Sequence
Protein Conformation Receptors Antigen T-Cell alpha-beta Genetic Vectors Molecular Sequence Data Histocompatibility Antigens Class II Immunoglobulin Variable Region Transfection Enterotoxins Epitopes Mice Structure-Activity Relationship Mutagenesis Site-Directed Animals Humans Peptides |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 150(6) |
| ISSN: | 0022-1767 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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