Polymorphism of the Apl (Neu-1) locus in the mouse.
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Biomedical subjects
Publications and source records attributed to J Klein.
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Twenty-nine randomly chosen, soluble antigens, many of them highly complex, were used to immunize mice of two strains, C3H and B10.RIII. Lymph node cells from the immunized mice were restimulated in vitro with the priming antigens and the proliferative responses of the cells was determined. Both strains were responders to 28 of 29 antigens. Eight antigens were then used to immunize 11 congenic strains carrying different H-2 haplotypes, and the T-cell proliferative responses of these strains were determined. Again, all the strains responded to seven of the eight antigens. These experiments were then repeated, but this time antibodies specific for the A (A alpha A beta) or E (E alpha E beta) molecules were added to the culture to block the in vitro responsiveness. In all but one of the responses, inhibition with both A-specific and E-specific antibodies was observed. The response to one antigen (Blastomyces) was exceptional in that some strains were nonresponders to this antigen. Furthermore, the response in the responder strains was blocked with A-specific, but not with E-specific, antibodies. The study demonstrates that responses to antigens not controlled by Ir genes nevertheless require participation of class II Mhc molecules. In contrast to Ir gene-controlled responses involving either the A- or the E-molecule controlling loci (but never both), the responses not Ir-controlled involve participation of both A- and E-controlling loci. The lack of IR-gene control is probably the result of complexity of the responses to multiple determinants. There is thus no principal difference between responses controlled and those not controlled by IR genes: both types involve the recognition of the antigen, in the context of Mhc molecules.
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One hundred and four H-2 congenic lines were typed for alleles at seven loci, Qa-1, Qa-2, Tla, C3, Ce-2, Pgk-2, and Upg-1, residing distal to the H-2 complex. The results of the typing were used to estimate the length of the segment of chromosome 17 derived from the donor strain of each line--that is, the minimal length of the differential segment. The results indicate that only lines derived by intra-H-2 crossing-over in such a way that they inherited the right-hand portion of H-2 from the inbred partner have the telomeric half of chromosome 17 identical with that of the inbred-partner strain. In other lines the differential segment is at least 3 to 10 cM long. It is argued that in some lines the entire telomeric half of chromosome 17 might be of donor-strain origin.
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Acrylamide gel electrophoresis of mouse urine distinguishes two groups of pepsinogens, the fast-migrating group A and the slow-migrating group B. Inbred mouse strains fall into two categories with respect to group B pepsinogens, one expressing a single-banded and the other a double-banded phenotype. This variation is controlled by a single locus, urinary pepsinogen-2 or Upg-2, which has at least two alleles, Upg-2s and Upg-2d. Typing of recombinant inbred strains suggests that the location of the Upg-2 locus is on chromosome 1, in the vicinity of loci coding for other peptidases, namely, Pep-2 and Rnr, and of the Acf-1 locus.
Two Icelandic sheep with clinical signs of visna appearing 6-7 years after intracerebral infection with visna virus were killed, fixed by perfusion and the central nervous system lesions examined by light and electron microscopy. Both sheep showed similar pathological changes. In the brain there was a severe periventricular inflammatory process with small foci of liquefaction necrosis and scattered small granulomas. In some areas of inflammation there was evidence of primary demyelination but it was not prominent. In the spinal cord there were focal plaques of primary demyelination. At the ultrastructural level the spinal cord lesions showed unambiguous primary demyelination with many naked axons; various stages of remyelination with peripheral type of myelin were also common. These observations indicate that the CNS lesions of visna, as seen in Icelandic sheep, fall into two categories: (a) an inflammatory process which often begins within weeks of infection and which occurs in the majority of infected animals in the absence of clinical paresis; and (b) focal demyelinating lesions of the spinal cord which are seen in sheep with clinical paresis but are uncommon in animals prior to onset of clinical signs. Both types of lesions may coexist.
Unanesthetized Jersey cows were studied during both pregnant (5-9 months) nonlactating states, and nonpregnant lactating states; and also following treatment with progesterone (Pr). The pH, PCO2 and PO2 of aortic blood, VE and f were measured and the mixed expired gas was analyzed. The following significant changes from the nonpregnant state occurred during pregnancy: PaCO2 = -3.2 mm Hg, pHa = +0.02 unit, VT = -0.44 L, f = +7 breaths/min, and VE/VCO2 = +9.7. Concomitant with the respiratory studies, serum Pr levels were determined by radioimmunoassay (RIA) in 11 nonpregnant and 5 pregnant cows, and in 6 nonpregnant, lactating cows prior to and on days 3, 5 and 10 of treatment with Pr (500 mg, i.m., twice daily). Minute ventilation (VE, L X min-1 X kg-1, BTPS) was positively correlated (r = +0.59) and PaCO2 was negatively correlated (r = -0.64) with endogenous serum Pr levels of non-pregnant and pregnant cows. However, exogenous Pr did not significantly alter these parameters or pHa, despite mean serum levels nearly twice (23.6 +/- 10.2 ng/ml) those observed in pregnant cows (12.7 +/- 3.7 ng/ml). The increased ventilation during pregnancy in Jersey cows, shown in this study, does not appear to be related to Pr as exogenous Pr failed to induce hyperventilation. The correlation of increased ventilation with endogenous Pr levels therefore suggests that the mode of in vivo Pr release, or different compound, simultaneously released, could be the stimulus.
Icelandic sheep were injected intracerebrally with visna virus, which produces a persistent infection of the CNS accompanied by encephalomyelitis and focal demyelinating lesions. Studies were conducted on two groups of sheep, with short-term infections (25 sheep sampled 1-3 months after infection) and long-term infections (14 sheep sampled 5-6 years after infection). Quantitative determination of CSF immunoglobulin levels 5 years after infection indicated that IgM concentration was usually elevated, IgG2 was occasionally elevated and IgG1 was rarely elevated. CSF oligoclonal bands were seen in about half the sheep examined 5 years after infection. There was a correlation between high titers of CSF antiviral antibody and both elevated CSF IgM concentration and CSF oligoclonal bands. Serum/CSF IgG1 ratios indicated that the blood-brain barrier was apparently intact in long-term visna infection, consistent with intrathecal synthesis of IgM and of antiviral antibody. The alterations in CSF immunoglobulins in visna resemble those found in other persistent CNS virus infections and in multiple sclerosis.
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Ab initio molecular orbital calculations with the 3-21G basis set show the most stable dilithiopropene structure to be the di-pi lithium-bridged structure VI of 1,3-dilithiopropene. This structure is most simply regarded as an ion triplet of two lithium cations and a propenylidene dianion.
H-2 haplotypes were extracted from wild mice of three subspecies, Mus musculus domesticus, M. m. molossinus, and M. m. castaneus, that are known to have been separated from one another for some 1 to 2 million years. Serologically indistinguishable molecules controlled by some of the polymorphic H-2 loci were compared by tryptic peptide mapping, and the maps were found to be identical. In addition, a number of instances of biochemically indistinguishable H-2 molecules were found among wild mice and inbred strains of the M. m. domesticus subspecies. These findings suggest that some of the H-2 alleles have not altered for greater than 1 million years. To reconcile this apparent stability of H-2 genes with their extraordinary polymorphism (some 100 alleles at each of the polymorphic H-2 loci), it is proposed that the H-2 alleles evolve as if they were separate loci.
To test the hypothesis that the H-2 polymorphism is adaptive, the degree of polymorphism of loci linked to the H-2 complex on chromosome 17 of the house mouse was compared to the degree of polymorphism of loci located on other chromosomes. Published theoretical analyses show that polymorphisms subject to natural selection usually reduce the polymorphism of linked neutral loci. The first test of the hypothesis was based on data obtained from a survey of the polymorphism of 12 isozyme-encoding loci in wild house mice from Europe, North Africa and South America. Results of this test showed that, on the average, H-2 linked loci were as polymorphic as loci located on other chromosomes. In fact, the data suggested that H-2 linked loci might be more polymorphic than other loci. To test this hypothesis more rigorously, data for the 12 isozyme-encoding loci were augmented with data from published surveys of the polymorphisms of 59 loci in house mice from Europe and North America. Results of these tests showed that polymorphic loci linked to the H-2 complex tended to be more, rather than less, polymorphic than loci located on other chromosomes. The cluster of highly polymorphic loci seems to be related to linkage of these loci to the highly polymorphic H-2 complex, but the way in which the influence is exerted could not be readily explained.
The role of the Ek (E alpha kE beta k) molecule in the generation of suppressor T (Ts) cells specific for lactate dehydrogenase B (LDHB) was studied using different approaches. First, lymph node cells from LDHB-primed B10.A(2R) (AkEk) nonresponder mice were shown to suppress the LDHB-specific and Ak-restricted proliferative response of T cells from the congenic responder strain B10.A(4R), which does not express E molecules (AkEo). Similarly, lymph node cells from primed CBA (AkEk) mice suppressed the anti-LDHB response of Lyt-1+Lyt-2-T cells (depleted of Lyt-2-bearing Ts cells) from the same mice. Second, in vitro priming of 2R (AkEk) T cells with LDHB-pulsed 4R (AkEo) antigen-presenting cells (APC) generated T-cell proliferation but not suppression. Third, nonresponder 2R mice were turned into responders by injecting them with LDHB-pulsed 4R APC or monoclonal Ia.m7 antibody that blocks the Ek molecule. The data demonstrate that expression of Ek molecules by the APC is necessary to generate LDHB-specific Ts cells, which in turn prevent the proliferation of Lyt-1+Lyt-2- (probably helper) cells recognizing the same antigen in the context of the Ak molecule.