title: The expressed T cell repertoire is hierarchical: the precise focus of lysozyme-specific T cell clones is dependent upon the structure of the immunogen.
abstract: The breadth of the expressed T cell repertoire to antigens under Ir gene regulation is central to the understanding of Ir gene function. While major histocompatibility complex (MHC)-related differences in the elicited T cell repertoire are readily demonstrated, the reasons for the choice of particular determinants are not clear. It is commonly assumed that the Ia molecules as the sole products of Ir genes somehow influence the choice of determinants selected for response. That this choice can be severely restricted in the C57BL/6 mice to hen egg-white lysozyme (HEL) was shown earlier with L2 (a.a. 13-105) immunization. L2, as the major cyanogen bromide cleavage fragment of HEL represents about 70% of the whole molecule and contains all the determinants recognize by proliferative T cells induced with HEL in this strain. All clones obtained from L2-immunized B6 mice recognized HEL and determinants available only within the T11 peptide (a.a. 74-96), suggesting that the entire T cell repertoire was restricted to determinants within the T11 region for HEL [1]. To test this hypothesis, long-term T cell lines were derived from HEL-immunized B6 mice. Bulk HEL- and L2-induced T cell lines showed similar L2-specific responses. However, in contrast to clones from the L2-lines, which were all specific for T11, the large majority of clones from the HEL-induced lines were specific for "non-T11" determinants. Antigen recognition of all clones was restricted by a similar restriction element on the I-Ab molecule. Thus, T cells directed against "non-T11" determinants available on the L2 fragment were not induced by L2 itself but required the whole molecule. The evidence clearly shows that within the T cell repertoire, the selection of clones is dramatically changed by the context in which the determinants are available. In fact, a hierarchy of T cells specific for T11 and "non-T11" determinants results. Structural differences between HEL and L2 lead to an inversion of this hierarchy. As both the HEL- and L2-induced lines were maintained and cloned under identical conditions, this appears to reflect the cellular interplay that occurs during the early in vivo selection period, rather than during the later in vitro activation and propagation of the lines and clones derived from them. The direct implications of these findings relate to interpretations of Ir gene phenomena.(ABSTRACT TRUNCATED AT 400 WORDS)
mesh_terms: D000818:Animals; D002999:Clone Cells / Q000276:immunology; D000939:Epitopes; D005802:Genes, MHC Class II; D008285:Major Histocompatibility Complex; D051379:Mice; D009113:Muramidase / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000939:Epitopes; D009113:Muramidase