An unusual clonotypic determinant on a cytotoxic T lymphocyte line is encoded by an immunoglobulin heavy chain variable region gene.
We have detected, in a CTL clone, an mRNA homologous to an immunoglobulin heavy chain variable region (VH) gene segment. A full-length copy of this mRNA was cloned and sequenced, revealing that it is the transcript of an authentic, unrearranged VH gene. The predicted protein product of this expressed VH gene is an approximately 12-kilodalton polypeptide, with secretory signal peptide leader and no membrane-anchoring sequences. Using immunologic reagents generated against a synthetic peptide representing the carboxyl terminus of the VH protein, we detect this protein as a clonotypic cell surface molecule. Strikingly, the anti-peptide reagents also exert effects on CTL function clonotypically. Immunoprecipitation experiments suggest that the VH protein may be associated noncovalently with the consensus, major histocompatibility complex-restricted, antigen-specific T cell receptor alpha- and beta-chains on the cell surface of this CTL. We detect weakly cross-reactive material similar to the VH protein in electrophoretic mobility in other CTL clones and suggest the possibility that small VH-like molecules may constitute a novel class of receptor components with variable determinants involved in the binding of nominal antigen and contributing to overall receptor diversity.
D S
DS
Ucker
Y
Y
Kurasawa
S
S
Tonegawa
D000818:Animals; D000906:Antibodies / Q000502:physiology; D002460:Cell Line; D002999:Clone Cells / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D000939:Epitopes / Q000032:analysis / Q000235:genetics*; D005260:Female; D005796:Genes; D007143:Immunoglobulin Heavy Chains / Q000235:genetics* / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008811:Mice, Inbred DBA; D010446:Peptide Fragments / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism
D000906:Antibodies; D000939:Epitopes; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D010446:Peptide Fragments; D012333:RNA, Messenger