Gene transfer directly demonstrates a role for TCR V alpha elements in superantigen recognition.
Recent structure-function studies of ours and others indicating that regions of the TCR other than V beta are involved in the TCR-superantigen (SAg)-MHC class II trimolecular interaction were correlative; thus, while the conclusions were persuasive, they were not unequivocal. The transfection experiments described in this report show that 1) responsiveness to staphylococcal enterotoxin B in V beta6 T cells was transferred by a V alpha4- but not by V alpha8- and V alpha10-containing alpha-chain cDNA constructs, 2) responsiveness was not transferred by a chimeric alpha-chain construct containing the N and J regions from a responsive T hybrid clone and the V alpha10 V alpha region from a nonresponsive clone, and 3) responsiveness was transferred by a chimeric alpha-chain construct in which most of the V alpha region (from the N terminus to the C-terminal end of the complementarity-determining region 2) was derived from the V alpha4 alpha-chain of a responsive T hybrid and the rest (framework 3, N, and J) from the V alpha8 alpha-chain of a nonresponsive T hybrid. Thus, these data provide the first direct evidence for a specific SAg response facilitating activity in a defined V alpha segment and map this activity N-terminal of framework region 3. Furthermore, the diversity in the alpha- and beta-chain junctional regions of a panel of staphylococcal enterotoxin B-responsive V beta6 T hybrid clones excludes a stringent corequirement for a particular junctional region for the V alpha4 segment to mediate its facilitating activity. Finally, a model postulating a universal role for V alpha elements in TCR recognition of SAg is presented.
Donson
D
D
Department of Surgery, North Shore University Hospital, New York University Medical College, Manhasset 11030, USA.
Borrero
H
H
Rutman
M
M
Pergolizzi
R
R
Malhado
N
N
Macphail
S
S
D000818:Animals; D002478:Cells, Cultured; D018014:Gene Transfer Techniques; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D051379:Mice; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*; D018089:Superantigens / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D007135:Immunoglobulin Variable Region; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens