Nature and characteristics

Classically described cytotoxic T cells are class I MHC-restricted (i.e. foreign antigen is recognized in the context of H2-K, D or L molecules in the murine system and HLA-A, B or C in the human). These effectors also express the cell surface molecules Thy-1, Lyt-1, Lyt-2,3 (CDS), TCRap, CD3 and LFA-1. In the 1980s, it was then reported in the human for virus-specific CTLs and subsequently confirmed in the murine model that class II MHC-restricted CTLs are elicited in response to viral antigens. These effectors bear the cell surface molecules Thy-1, Lvt-1, LFA-1, L3T4 (CD4), CD3 and TCRctp. Concomitant with these reports, the suggestion was independently put forth that Lyt-2 (CD8) and L3T4 (CD4) expression are more clearly correlated with class 1 and class II MHC restriction, respectively, than with cytotoxic effector and helper functions, respectively. Exceptions to the rule have been found (e.g. Lvt-2+ class II MHC-restricted CTLs), but the correlation holds for the bulk of CTLs. The class II MHC-restricted CTLs may have been overlooked in earlier studies because many tumor cell and fibroblast cell lines and macrophages used as target cells did not express class II MHC molecules. Target cells for human CTLs, however, are usually EBV-transformed B lymphoblastoid cell lines (LCL), which generally express class II MHC molecules.

Clonal CTL populations have been mapped for their MHC restriction molecule by comparing lysis of class 1 MHC-bearing targets with targets which bear both class I and class II MHC molecules (e.g. B lymphoma cells). Transfected murine ccll lines where a given class I or class II MHC molecule is expressed in a cell bearing MHC molecules of a different haplo-type have proven useful as target cells to map MHC restriction. In the human, homozygous typing lines have been used as targets, but the serological classification of class I and class II MHC molecules does not always help to distinguish restriction molecules recognized by CTLs. Transfected murine fibroblast lines which express human class I or class II MHC molecules have proven useful in these cases. Antibodies directed towards the class I or class II MHC molecules generally inhibit the cytolysis of specific target cells (antibodies directed towards the foreign antigen generally do not inhibit). In addition, antibodies directed to CD 8 or CD4 molecules have been shown to inhibit cytolysis by class I MHC-restricted and class II MHC-restricted T cells, respectively. Anti-LFA-1 specific antibodies block cytolysis mediated by either CD8" or CD4+ CTLs.

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