Lafuse, William P.

Abstract Mouse alloantiserum capable of detecting minor histocompatibility antigens has been produced. Cytotoxic antibody to products of the H-4 locus was produced by reciprocal immunization of minor H loci congenic strains B10 (H-4a) and B10.129(21M) (H-4b), with mitogen-stimulated lymphocytes and epidermal cells. Absorption studies suggested antibodies to more than 1 specificity. The antibodies cross-react with products of other minor H loci. Alloantiserum to the H-4 gene product precipitates a glycoprotein with a m.w. of approximately 45,000 from radiolabeled Con A-stimulated lymph node cells.

Abstract Recombinant D2.Gd (KdAdBbJbEbCbSbDb) was derived from parental strains B6 (H-2b) and DBA/2 H-2d). Recent peptide studies and 2-D electrophoresis studies from other laboratories have shown that the Aed (E beta) chain of D2.GD is structurally different from the parental-derived chain. An antiserum (D2.GD X A. TFR5)F1 anti-DBA/2 was produced that detects an Ia specificity (Ia.50) in the I-E molecule formed by the parent Aed chain and lacking in the I-E molecule formed by the variant Aed. chain. The variant Ae chain could have derived either from a mutational event or an intracistronic cross-over.

Abstract Pretreatment of mice genetically susceptible to type II collagen-induced arthritis (CIA) with monoclonal or polyclonal antisera specific for I region gene products (Ia antigens) suppressed or delayed the onset of CIA, whereas pretreatment with anti-Ia to an irrelevant haplotype was without effect. The humoral response to type II collagen was transiently depressed 14 days after immunization but antibody levels did not differ significantly after 28 days. The peak delayed-type hypersensitivity to type II collagen was unaffected by anti-Ia treatment. Monoclonal antibody of one anti-Ia specificity enhanced both the antibody response and the arthritis incidence in one mouse strain.

Abstract Ia specificities 22 and 23 were initially identified by using conventional alloantisera and were mapped to the I-E subregion of k and d haplotypes on the basis of their reactivity with selected recombinants. Recently we found that Ia 22 and 23 are hybrid determinants on the basis of their expression on selected F1 cells, but absence from both parental cells. Initial attempts to detect hybrid Ia antigens by immunizing parents with F1 cells were unsuccessful. By utilizing lipopolysaccharide (LPS)-stimulated F1 spleen lymphoblasts as immunogens, 1 of the parents as recipient and the other parent cells for absorption of antisera, specific anti-Ia.22 and 23 antibodies were produced. The specificity of these parent anti-F1 sera was confirmed by cytotoxic and immunoprecipitation analyses.

Abstract The I-E molecule is produced by complementation of genes in I-A (Ae) and I-E (E alpha). Ia specificities 22 and 23 are generated by the hybrid molecule, whereas Ia.7 is an allotypic determinant presumably on the alpha-chain of the I-E molecule. Recombinant A.TFR5 (AfEk) lacks detectable I-E molecule since Af and Ek cannot complement. In a cross between A.TFR5 and B10.A(4R) (AkEb), Aek and E alpha k can successfully complement to express the I-Ek molecule on the cell surface of the heterozygote. Haplotypes H-2b and H-2s can also provide the permissive Abe and Ase molecules for complementation with Ek alpha of A.TFR5.