Specificity for molecules of the major histocompatibility complex mediated by a hybrid immunoglobulin-T cell receptor.
A chimeric T-cell receptor (TCR) alpha-chain gene was produced by shuffling the immunoglobulin VDJH from a 40-140 digoxin-specific hybridoma onto alpha-chain constant region (C alpha) exons. This hybrid immunoglobulin-TCR gene was used to produce transgenic mice. Previous results indicated that this chimeric gene encoded a polypeptide that associated with endogenously encoded beta chains to form a hybrid TCR. T cells expressing this receptor could be stimulated with antibodies specific for CD3 or the 40-140 idiotype (Id40-140), and also with digoxin coupled to bovine serum albumin (digoxin-BSA). We were interested in determining whether a hybrid receptor such as this could also recognize the natural ligand of T cells, namely allelic variants of major histocompatibility complex (MHC) molecules. A T-cell hybridoma was produced that expressed a hybrid receptor with specificity for an IAk-encoded determinant, digoxin-BSA, or staphyloccocal enterotoxin B. Transfection experiments showed that the specificity for MHC determinants was dependent on both the hybrid alpha chain and a particular beta chain. These results indicate that a V beta domain combined with a VH domain can produce a receptor capable of reacting with MHC molecules, and at the same time retain specificities mediated by the beta chain and alpha chain alone. A conclusion is that the pervasive MHC specificity of the TCR is not unique to the family of TCR heterodimers, but is selected, and can be mediated by immunoglobulin domains.
Kawasaki
H
H
Department of Biology, University of California, San Diego, La Jolla 92093-0063.
Becker
M L
ML
Hedrick
S M
SM
D000818:Animals; D030801:Animals, Genetically Modified; D000917:Antibody Formation; D004274:DNA, Recombinant; D000939:Epitopes; D005434:Flow Cytometry; D015870:Gene Expression; D006825:Hybridomas; D007143:Immunoglobulin Heavy Chains; D007130:Immunoglobulin Idiotypes / Q000096:biosynthesis; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000276:immunology*; D008285:Major Histocompatibility Complex / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta
D004274:DNA, Recombinant; D000939:Epitopes; D007143:Immunoglobulin Heavy Chains; D007130:Immunoglobulin Idiotypes; D007135:Immunoglobulin Variable Region; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta