Thy-1 dull ␥␦ T cells constitute a distinct adult ␥␦ T cell subset characterized by the expression of a TCR composed of V␥1C␥4 and V␦6C␦ chains with limited junctional sequence diversity. However, several features of the expressed Thy-1 dull TCR-␥␦ genes, in particular the absence or minimal presence of N region diversity and the almost invariable D␦2-J␦1 junction, are typical of rearrangements often found in the fetal thymus. In this study, we have investigated the origin of these cells. Few Thy-1 dull ␥␦ thymocytes developed in syngeneic radiation adult chimeras, regardless of whether the recipient mice were given adult bone marrow or fetal liver cells as a source of hemopoietic precursors. In contrast, normal numbers of Thy-1 dull ␥␦ T cells developed in fetal thymi grafted into adult syngeneic recipients. Interestingly, the majority of Thy-1 dull ␥␦ thymocytes present in the grafts were of graft origin, even when most conventional ␥␦ and ␣␤ thymocytes in the grafted thymi originated from T cell precursors of recipient origin. Single-cell PCR analyses of the nonselected TCR-␥ rearrangements present in adult Thy-1 dull ␥␦ thymocytes revealed that more than one-half of these cells T o recognize and respond specifically to a vast array of foreign Ags, the immune system has developed several mechanisms to diversify the repertoire of Ag-specific receptors generated through V(D)J recombination (1). Thus: 1) the use of different germline gene segments, 2) their imprecise joining during the recombination process driven by the action of nucleases that process the ends of the gene segments and by the templateindependent polymerase TdT that adds nucleotides at the same ends before ligation, and 3) the combinatorial association of the proteins produced by the recombination process allows a potential diversity that has been estimated to comprise 10 11 Ig receptors, 10 16 TCR-␣␤, and 10 18 TCR-␥␦ (2). Early in ontogeny, the diversity of the newborn T and B cell repertoires is particularly restricted, as a result of the small number of T and B cell clones and the absence of some of the diversification mechanisms that operate later in ontogeny. For example, TdT is not expressed in fetal hemopoietic organs and is first detected in developing thymocytes 3-5 days after birth (3, 4). Consequently, Ig and TCR chains formed during fetal and early postnatal life lack significant N region addition (5-9). Furthermore, the appearance of predominant junctional sequences among fetal Ig H chain rearrangements correlates with the presence of short homology repeats near the ends of the coding segments (5, 10). Together with an apparent gene segment usage bias (5, 11, 12), these mechanisms result in the formation of a limited repertoire of Ig and TCRs biased for germline-encoded specificities. The advantage of this restriction may be the selection and maintenance in the germline of protective Ab specificities (13) and of more promiscuous TCR specificities that allow a relatively small number of T cells to protect against a broad range of pa...

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Mice with functionally deleted genes encoding MHC class I heavy (H-2K(b), H-2D(b)) and light (beta2-microglobulin) chains were used in bone marrow cell transfer experiments to study the role of class Ia and Ib molecules in NK cell function. Absence of H-2K(b) and absence of H-2D(b) on bone marrow cells resulted in complete and in almost complete NK-mediated rejection, respectively. Absence of either H-2 class Ib (at least when expressed in H-2 class Ia-deficient mice) or cell surface class Ia free heavy chains did not result in bone marrow rejection. Thus, in C57BL/6 adult mice, the inactivation of NK cells required for bone marrow cell engraftment relies entirely upon-H-2 class Ia molecules. These results imply the existence of an inhibitory receptor which recognizes either directly or indirectly H-2D(b) molecules and further suggest that in C57BL/6 mice the NK cells which do not express a H-2K(b) specific inhibitory receptor necessarily express an H-2D(b)-specific one.