HSV-1 glycoprotein I-reactive TCR gamma delta cells directly recognize the peptide backbone in a conformationally dependent manner.
Despite the description of numerous antigenic ligands recognized by TCRgammadelta cells, detailed information concerning the structural nature of these antigenic epitopes is lacking. In addition, the recent descriptions of human TCRgammadelta cells recognizing mycobacterium-derived low m.w. lipid molecules confirms that the spectrum and nature of biologic structures that are capable of being recognized by TCRgammadelta cells are unclear. We have previously described a murine TCRgammadelta cell clone, TgI4.4, that is reactive to herpes simplex virus (HSV)-1 glycoprotein I (gI). Unlike TCRalphabeta-mediated, MHC-restricted Ag recognition but similar to Ig Ag recognition, TgI4.4 recognizes purified gI directly, in the absence of Ag processing or presentation. Since gI is a complex glycoprotein, the nature of the antigenic epitope was investigated. First, gI recognition by TgI4.4 is conformationally dependent, as revealed by denaturation and proteolytic experiments. Secondly, the epitope recognized by TgI4.4 was mapped to the amino terminus by using insertion mutants of gI. Lastly, TgI4.4 recognizes the gI protein directly since completely deglycosylated forms of gI are efficiently recognized. Therefore, TCRgammadelta cells are capable of recognizing a variety of molecular structures, including proteins. The ability of TgI4.4 to recognize a nonglycosylated form of gI suggests that HSV-1 recognition by TCRgammadelta cells in vivo is not limited by cell-specific glycosylation patterns or glycosylation-dependent conformational influences.
Sciammas
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Committee on Immunology, Ben May Institute for Cancer Research, University of Chicago, IL 60637, USA.
Bluestone
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JA
D000818:Animals; D017951:Antigen Presentation; D016466:CHO Cells; D002236:Carbohydrate Conformation; D050260:Carbohydrate Metabolism; D002241:Carbohydrates / Q000276:immunology; D002999:Clone Cells; D006224:Cricetinae; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000378:metabolism; D018259:Herpesvirus 1, Human / Q000276:immunology*; D006801:Humans; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D011487:Protein Conformation; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism
D002241:Carbohydrates; D018984:Epitopes, T-Lymphocyte; D010446:Peptide Fragments; D016692:Receptors, Antigen, T-Cell, gamma-delta; D014759:Viral Envelope Proteins; C064959:glycoprotein I, herpes simplex virus type 1