Meiotic recombination within the H-2K-H-2D interval: characterization of a panel of congenic mice, including 12 new strains, using DNA markers.

Intra-H-2 recombinant congenic strains are widely used to localize traits to specific subregions of the major histocompatibility complex and have provided evidence for the existence of meiotic recombinational hotspots in mammals. Forty-seven intra-H-2 recombinant strains, including 12 not previously reported, have been identified by serological typing in our laboratory. We have extended the analysis of the crossover sites in these mice using DNA markers for Ab, Aa, Eb, Ea, Cyp21-ps, D17Tu3, Bat7, and Bat5.

Transplantation effects of a unique major histocompatibility complex class I mutation.

This study describes a novel MHC class I mouse mutant that was discovered because of loss of reactivity of its cells to monoclonal antibodies. The mutation occurred in the H-2Ks molecule and is the first in vivo mutation described that has a single altered amino acid residue (amino acid 107) distant from the regions considered to be peptide or TCR contacts. Nevertheless, skin grafts from the mutant to the parent are rejected by CD8+ T-cells.

Greying with age in mice: relation to expression of murine leukemia viruses.

Some strains of C57BL/10 H-2-congenic mice were found to exhibit greying with age, whereas others did not. Two patterns of greying were observed, diffuse greying beginning at 4 to 6 months of age and patterned greying beginning at 4 to 6 weeks. Strains exhibiting either greying pattern expressed high levels of infectious ecotropic and mink cell focus-inducing murine leukemia viruses (MuLV) in tests of thymus and spleen and in cultures from skin or tail biopsies, whereas nongreying strains expressed little virus until late in life.

Relationship between a retroviral germ line reintegration and a new mutation at the ashen locus in B10.F mice. Retroviral integration and an ashen mutation.

In a litter of B10.F mice a single mouse was found with a "dilute-like" coat-color mutation. F2 matings were then carried out to establish sufficient numbers of mice carrying this mutation in a homozygous form.

Control of the immune response to the EA-2.1 alloantigen of the mouse by the H-2 complex.

The immunization of selected congenic strains and hybrids with the Ea-2.1 cellular alloantigen of the mouse shows that the anti-Ea-2.1 immune response is regulated by a gene or genes associated with the H-2 gene complex.

Antigen-specific soluble helper activity for murine major histocompatibility complex-encoded molecules. I. Kinetics of factor production after skin transplantation and genetic mapping of the H-2 region specificity.

Antigen-specific soluble helper molecules are produced during major histocompatibility complex-disparate allograft priming. Genetic mapping studies with appropriate recombinant and mutant lines of mice have defined the antigen specificities of the soluble helper molecules described here as being directed against the H-2Dd molecules. The production of antigen-specific helper molecules is a relatively early event after H-2Dd-region allograft priming.

Gene dose effects in Ir gene-controlled systems.

(B10.A x B10.S)F1 hybrid mice produce lower levels of anti-GL phi antibody than B10.

Gene complementation in the T-lymphocyte proliferative response to poly (Glu55Lys36Phe9)n. A demonstration that both immune response gene products must be expressed in the same antigen-presenting cell.

The immune response (Ir) to the random copolymer GLphi depends upon the function of two Ir genes, Ir-GLphi-beta[beta] and Ir-GLphi-alpha[alpha], mapped to the I-A and I-E/C subregions of the major histocompatibility complex, respectively. In this paper, the site(s) of expression of the products of these two Ir genes was examined by evaluating T-lymphocyte proliferative responses of bone marrow radiation chimeras. Chimeras were created in [alpha+beta- X alpha-beta+]F1 responder mice by lethal irradiation and reconstitution with a mixture of bone marrow cells from both parental strains.

Ir-genes in H-2 regulate generation of anti-viral cytotoxic T cells. Mapping to K or D and dominance of unresponsiveness.

H-2 dependent and virus-specific Ir genes regulate the generation of primary virus-specific K or D restricted cytotoxic T-cell responses in vivo. The following examples have been analyzed in some detail: first, Dk restricted responses to vaccinia in Sendai viruses are at least 30 times lower than the corresponding K-restricted responses irrespective of the H-2 haplotypes (k, b, d, dxs, dxq) of K and I regions; in contrast, LCMV infection generates high responses to Dk. These findings are consistent with but do not prove that this Ir gene maps to D.

Coupled complementation of immune response genes controlling responsiveness to the H-2.2 alloantigen.

The ability of various B10 congenic resistant strains to respond to the alloantigen H-2.2 was tested. High and low antibody-producing strains were distinguished by their anti-H-2.

Gentic control of the immune response to the Ea-2 alloantigen system of the mouse. I. The humoral antibody response.

The immunization of selected congenic strains and hybrids against the Ea-2.1 cellular alloantigen of the mouse demonstrated that the hammagglutinating antibody response to Ea-2.1 is regulated by a gene or genes associated with the H-2 gene complex.

Characterization of immune response and mixed lymphocyte reactions in selected intra-H-2 recombinant strains.

The genes controlling the immune response to the random linear terpolymers GAT and GLpro have been mapped in the Ir-1A or Ir-1B subregions with five lines of H-2-s/H-2-a recombinant mice. The I region also contains a third subregion, I-C, which codes for a lymphocyte-activating determinant, Lad2, controlling mixed lymphocyte reactivity. The mixed lymphocyte responses associated with I-C region disparity are compared with the stimulation noted with other H-2 region differences.

Host genetic control of recovery from Friend leukemia virus-induced splenomegaly: mapping of a gene within the major histocompatability complex.

The influence of the major mouse histocompatibility gene complex (H-2) on the response of mice to Friend leukemia virus was studied in F(1) congenic mice differing only at genes within the H-2 complex. F(1) mice which were H-2(b/b) had a high incidence of recovery from splenomegaly compared to H-2(b/d) or H-2(b/a) mice. In mice with recombinations within the H-2 complex a gene (designated RFV-1), responsible for the Friend virus recovery effect, was found to map near or within the D region of serologically detectable transplantation antigens.

Cell-mediated lympholysis. Importance of serologically defined H-2 regions.

The cell-mediated lympholytic capability of mouse spleen cells stimulated in mixed lymphocyte culture is related to the major histocompatibility complex genotype on target lymphocytes. The strain combinations AQR-B10. T(6R) and B10.

H-2-linked immune response (Ir) genes. Independent loci for Ir-IgG and Ir-IgA genes.

Two H-2-linked autosomal dominant immune response (Ir) genes Ir-IgG and Ir-IgA were demonstrated to be at separate loci. Ir-IgG controls the immune response to IgG (gamma2a) myeloma proteins and Ir-IgA the immune response to IgA meyloma proteins. Both genes are associated with the H-2K region specificities of the H-2 chromosome, specifically Ir-IgG with H-2(b) and Ir-IgA with H-2(a).

Genetic control of the immune response. Mapping of the Ir-1 locus.

Eleven strains of mice bearing recombinant H-2 chromosomes derived from known crossover events between known H-2 types were immunized with a series of branched, multichain, synthetic polypeptide antigens [(T,G)-A--L, (H,G)-A--L, and (Phe,G)-A--L]. Results with nine of the eleven H-2 recombinants indicated that the gene(s) controlling immune response to these synthetic polypeptides (Ir-1) is on the centromeric or H-2K part of the recombinant H-2 chromosome. Results with two of the eleven recombinant H-2 chromosomes indicated that Ir-1 was on the telomeric or H-2D part of the recombinant H-2 chromosome.