Repertoire development and ligand specificity of murine TCR gamma delta cells.

During the past several years, we have been studying the circulating TCR gamma delta cells expressed in peripheral lymphoid tissues. Biochemical and molecular characterization of the TCR gamma delta heterodimers present on these TCR gamma delta cells identified 3 TCR gamma proteins, V gamma 2-C gamma 1, V gamma 1.2-C gamma 2, and V gamma 1.1-C gamma 4. In addition, at least 6 different V delta gene products (V delta 2,4,5,6,V alpha 10, V alpha 11) are expressed in peripheral lymphoid tissue. Nucleotide sequence analysis has revealed a great deal of junctional diversity present among the different V gamma and V delta proteins. Thus, compared to other nonlymphoid tissues (e.g., skin), this population of TCR gamma delta cells appears quite extensive. The development and specificity of TCR gamma delta cells has been pursued by two approaches. First, different TCR gamma delta cells clones were generated which recognize MHC-encoded gene products. One clone recognizes an unconventional TL-encoded antigen, whereas others have been shown to recognize either classical MHC class I or class II antigens. The TCR gamma delta receptor genes have been cloned from the TL-specific TCR gamma delta cell and used to construct transgenic mice to examine the development of TCR gamma delta cells. Although the Tg+ TCR gamma delta cells are tolerized by thymic clonal tolerance similar to TCR alpha beta cells, the epithelial Tg+ TCR gamma delta cells are subjected to non-deletional tolerance (anergy). A second approach towards examining the development of TCR gamma delta cells has been to compare the repertoire of TCR gamma delta splenocytes in a variety of inbred and MHC-congenic strains of mice using subset-specific anti-murine TCR gamma delta mAb. The percentage of individual subsets of splenic TCR gamma delta cells differ widely between different inbred strains of mice due to both MHC- and TCR-encoded genetic differences. In summary, these studies provides a basis for understanding and determining the ligand(s) of the TCR gamma delta heterodimer and the factors which shape the peripheral TCR gamma delta repertoire.