Trinitrophenyl Reactive T-Cell Clones in Functional and Molecular Analysis of the HLA-D Region
A central role for major histocompatibility complex (MHC) molecules in presentation of non-MHC antigens to T lymphocytes is generally acknowledged. Among the seminal studies demonstrating this phenomenon were those of Shearer and associates demonstrating that recognition of mouse target cells by trinitrophenyl (TNP)-specific cytolytic T cells required genetic homologies between the killer and target cells at H-2 class I loci (rev., Shearer et al., 1976). This system, employing target cells surface modified by hapten conjugation, has proven particularly useful in subsequent studies of MHC restrictions on antigen recognition by human T lymphocytes. As in the mouse, recognition of TNP-modified target cells by hapten-specific cytotoxic T lymphocytes has appeared to involve restrictions for class I HLA homology (Shaw and Shearer, 1978). The data in human systems have been substantially less compelling, however, with evidence in some instances for effective interactions between target and killer cells that did not involve obvious class I HLA homologies (Shaw and Shearer, 1978; Seldin et al., 1979). In contrast to target cell recognition by cytolytic T-cells, recognition of antigen by helper T-cells has generally required genetic homology between antigen-presenting cells and helper T cells (or B cells and helper T cells) for class II loci of the MHC (rev., Thomas et al., 1977). Subsequently, clear exceptions have been documented with respect to correlations between functional activity and MHC restrictions for antigen recognition (rev., Rich et al., 1986). On the other hand, identification of a dichotomy of T lymphocytes, one subset of which expresses the CD4 molecule (L3T4 in mice) and the other of which expresses the CD8 molecule (Ly2 in mice), has led to a more convincing correlation between T-cell subset and MHC recognition requirements in antigen presentation. That is, recognition of non-MHC antigens by CD4+ (L3T4+) cells requires class II MHC homologies between T-cells and antigen presenting cells, whereas recognition by CD8+ (Ly2+) T-cells is MHC class I restricted (rev., Swain, 1983).
KeywordsMajor Histocompatibility Complex Major Histocompatibility Complex Class Genetic Homology Major Histocompatibility Complex Restriction Restricting Element
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