Transfer of putative complementarity-determining region loops of T cell receptor V domains confers toxin reactivity but not peptide/MHC specificity.
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.
Patten
P A
PA
Department of Microbiology and Immunology, Stanford University, CA 94305.
Rock
E P
EP
Sonoda
T
T
Fazekas de St Groth
B
B
Jorgensen
J L
JL
Davis
M M
MM
D000818:Animals; D001483:Base Sequence; D004768:Enterotoxins / Q000737:chemistry / Q000235:genetics*; D000939:Epitopes / Q000737:chemistry / Q000235:genetics; D005822:Genetic Vectors; D000949:Histocompatibility Antigens Class II / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000737:chemistry / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010455:Peptides / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D011487:Protein Conformation; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D013329:Structure-Activity Relationship; D014162:Transfection
D004768:Enterotoxins; D000939:Epitopes; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D007135:Immunoglobulin Variable Region; D010455:Peptides; D016693:Receptors, Antigen, T-Cell, alpha-beta; C026066:enterotoxin A, Staphylococcal; C031818:enterotoxin B, staphylococcal