The mechanisms responsible for the induction of I-J restrictions on third-order suppressor T cells (TS3) were analyzed. The I-J phenotype of the antigen-coupled cells used for priming restricted the specificity of the TS3 population. Thus, TS3 cells were only generated after priming with antigen-coupled I-J homologous cells. Identity at the I-JM (and I-E) subregions was sufficient for TS3 induction. Furthermore, priming of H-2 heterozygous mice with antigen-coupled parental cells generated TS3 that were restricted to the parental haplotype used for priming. The splenic cell population responsible for antigen presentation and induction of TS3 cells was fractionated. The cells involved in antigen presentation were found in the splenic adherent population and were absent in the fraction containing splenic nonadherent T and B cells. The subsequent activation and interaction of TS3 cells is also restricted by genes in the H-2 complex. The results are discussed in terms of a general mechanism responsible for the induction of restrictions in T helper and TS3 cells.
In the 4-hydroxy-3-nitrophenyl acetyl (NP) contact sensitivity system, the activity of third-order suppressor cells and their factors is restricted by H-2(I-J) and Igh linked genes. The present report analyzes the specificity of NP-specific Ts3 cells and factors derived from H-2 and Igh heterozygous (B6 X C3H)F1 mice. Two approaches were used. First, heterogeneous populations of F1 Ts3 cells were activated in vitro and then assayed in Ts3-depleted recipients which carried different combinations of H-2 and Igh alleles. The second approach was to hybridize the Ts3 cells and analyze the specificity of the F1-derived TsF3. The combined data demonstrated four functionally distinct populations of Ts3 cells. The activity of each population was restricted by a particular combination of H-2 and Igh haplotypes. Thus, Ts3 cells derived from F1 donors can demonstrate an apparent scrambling of H-2 and Igh restriction specificities. There was functional allelic exclusion of the H-2(I-J) and Igh determinants expressed on (B6 X C3H)F1 hybridoma-derived TsF3. Thus, TsF3 from each cloned hybridoma line expressed only one set of I-J and Igh determinants. Furthermore, there was a complete correlation between the I-J and Igh linked determinants expressed on TsF3 and the restriction specificity. In view of the recent findings on the molecular biology of the I-J region, an alternative interpretation of the role of I-J determinants on suppressor cells and factors is offered.
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