A theory on the differentiation of bone-marrow stem cells

Differentiation of pluripotent stem cells is viewed in parallel with maturation of lymphoid cells. Both processes share many features each occurring within a reticular framework with its component RE cells. RE cells are seen as providing control over stem cell differentiation in marrow thus minimizing stem cell competition by concentrating differentiation stimuli of a particular kind. The differentiation molecules are considered to be histocompatibility and tissue specific antigen components derived from aging or activated mature blood cells. They are probably low molecular weight glycoproteins. Evidence that histocompatibility antigens are of importance in cellular differentiation is presented. The hypothesis presupposes positive feedback mechanisms to bone-marrow with threshold responses being determined by RE cells.     

Relationship between measles HI titers and an MS susceptibility gene

Summary Recently published studies of formal linkage analyses strongly suggest that a multiple sclerosis susceptibility (MSS) gene is linked to the HLA region of the sixth chromosome. The objective of this analysis was to investigate whether or not the gene has any demonstrable relationship to the immune status with regard to measles within members of multiple-case MS families. Family members were HLA-typed, and levels of antibodies to measles were determined using the hemagglutination inhibition assay. Since a specific, HLA-defined haplotype within each family is presumably a marker for the MSS gene, family members were characterized as either carrying [(+) controls] or not carrying [(–) controls] the MSS gene by the presence of this specific haplotype. Twenty families were entered into the analyses. Results revealed that the mean titer to measles was not different between (+) and (–) controls, and that MS cases had significantly higher titers than both control groups combined.

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Zusammenfassung Vor kurzem veröffentlichte Studien über die formale Verbindungs-Analyse lassen sehr stark vermuten, daß ein Anfälligkeitsgen für Multiple Sklerose (MSS) mit der HLA-Region des sechsten Chromosoms verbunden ist. Es war das Ziel der Analyse, zu untersuchen, ob das Auftreten dieses Gens irgendeine nachweisbare Verbindung mit dem Immunestatus in bezug auf Masern unter den Mitgliedern von Familien mit mehrfachen Fällen von MS hat. Die Familienmitglieder waren HLA-Typen, und die Anzahl der Antikörper für Masern wurde durch die Hämagglutination-Inhibition-Probe bestimmt. Da ein spezifischer, HLA-bestimmter Haplotype innerhalb jeder Familie als Kennzeichen für das MSS-Gen angenommen wird, wurden die Familienmitglieder als Träger [(+)-Kontrolle] oder Nichtträger [(–)-Kontrolle] des MSS-Gens durch das Auftreten dieses spezifischen Haplotypen bestimmt. Zwanzig Familien nahmen an der Analyse teil. Die Resultate zeigten, daß der Durchschnittstiter für Masern zwischen den (+)- und (–)-Kontrollen nicht unterschiedlich war, und daß die MS-Fälle wesentlich höhere Titer hatten als beide Kontrollgruppen zusammen.

     

Perthes' disease: A new genetic hypothesis

We describe the sex and age distributions of the onset of Perthes' disease in our own and six other large published series. The mathematical features of these distributions, together with the evidence for familial aggregations, agree with the theory that the disease is autoaggressive in aetiology and that two genetically-distinctive groups are at risk. We consider the frequency of affected sides — left, right, bilateral — in our own and other series: concordance for affected side(s) within sibships suggests that laterality might be genetically determined. Following Gray et al. we believe that predisposition to the disease is polygenic and we propose a simple scheme — involving an X-linked ‘recessive’ factor and an autosomal homozygous allele in each genotype — that is reasonably consistent with the slender evidence.     

ST-16: A new Bw16 subtype present in Mexican-Americans

Using a large battery of Bw16, w38, and w39 antisera, a new variant of Bw16 has been identified in four unrelated Mexican-American families. The serologi pattern obtained is distinct from that for the Bw38, Bw39, and 8W57 antigens. Absorption studies confirm the existence of this new Bw16 subtype which we term ST-16. ST-16 is Bw6-associated, with antigen frequency estimated to be 2.5% in Mexican-Americans.     

HLA—DR／DQ，HLA—A／B与肺结核相关性研究

目的研究组织相容性白细胞抗原-DR／DQ、A／B（histocompatibility leukocyte antigen,HLA—DR／DQ,A／B）与肺结核之间的联系,探讨遵义市部分汉族人肺结核发病与HLA—DR／DQ,HLA—A／B基因相关性。方法选取36名已确诊肺结核的患者作为研究组,选取与研究组患者年龄、性别无统计学差异的100名健康人作为对照组,抽取外周血提取DNA。使用新型PCR—SSP方法对DNA进行HLA—DQ／DR,HLA—A／B等位基因位点的检测,结果进行SPSS10．0软件统计学处理,比较正常对照组和肺结核患者组间各等位基因频率分布,计算两组优势比（oddsratio,OR）。结果（1）共检测到HLA—DR位点上的13种等位基因,HLA—DQ位点上的7种等位基因,HLA—A位点上的10种等位基因,HLA—B位点上的20种等位基因。（2）HLA—DRB1＊16在患者组和正常对照组中的基因频率分别为6．9％和1．5％（OR=5．215,P=0．049）;HLA—A＊2在患者组和正常对照组中的基因频率分别为40．2％和9％（OR=18．87,P=0．000）;HLA—A＊24在患者组和正常对照组中的基因频率分别为8．3％和19．5％（OR=5．690,P=0．015）。结论HLA—DR＊16、HLA—A＊2基因表达与肺结核呈正相关,提示HLA-DR＊16、HLA-A＊2可能是肺结核的易感基因,HLA-A＊24基因在正常对照组中的表达明显高于结核患者组,其可能是肺结核患者发病的拮抗基因。     

Restriction of self-antigen presentation to cytolytic T lymphocytes by mouse peptide pumps

Transport of an immunogenic self-peptide from the second domain of the mouse major histocompatibility complex (MHC) H-2K^d class I molecule is blocked at the TAP1-TAP2 peptide pump level due to its amino acid sequence and is not presented to cytolytic T lymphocytes (CTL). We demonstrate that first, TAP1-TAP2 pumps can restrict antigen presentation by selecting against internal peptide motifs which are not involved in peptide binding to MHC class I molecules. Second, some molecules targeted to the endoplasmic reticulum are processed for MHC class I presentation in the cytosol. Third, some abundantly expressed immunogenic self-peptides are cytosolically sequestered. The advantage for the host, in terms of the peripheral T cell repertoire is that the spared CTL can be used to recognize foreign antigens. It is, however, anticipated that this advantage will be exploited by pathogens to evade immune surveillance by similar strategies.     

重组蛛丝蛋白支架材料在大鼠体内的组织相容性

目的探讨基因重组蛛丝蛋白等4种支架材料在大鼠体内的组织相容性。方法按照生物材料生物学评价试验国家标准进行4种材料的动物体内植入实验,通过大体观察和组织学方法对4种材料进行检测评价。结果4种材料组织相容性优良顺序为pNSR16、pNS2、PVA、pNSR-Z。pNSR16和pNS2支架材料均显示出良好的组织相容性。结论重组蛛丝蛋白有良好的组织相容性,其应用于组织工程的前景是广阔的。     

Is the MHC a general self-recognition system playing a major unifying role in an organism?

From the review of several recent observations of cell-cell interactions, which occur preferentially in autologous or syngeneic situations such as rosettes, adhesion, homing, and contact inhibition, the existence of an active general process of cellular self-recognition, not limited to the immune system, is postulated. This process is MHC associated or dependent, and seems to require an identity of ubiquitous molecules of class I--or other linked gene products at the surface of interacting cells. In contrast, class II molecules are not apparently implicated in general self-recognition. The immune system is regarded as a late evolution from a self-recognition system. It retains the ability of self-evolution, but possesses the exclusive property of active discrimination against foreignness. The astonishing fact that identity of MHC products seems to be needed for recognition is discussed in the context of various possible mechanisms. From immunological and genetical consideration, it is proposed that the genuine biological role of the MHC would be that of a self-recognition and unifying system.     

Mapping and definition of HLA class I and II serologic epitopes using an unbiased reverse engineering strategy

Current models describing HLA epitopes are both theoretical and empirical. Each has limitations yielding discordant results and increasingly complex modeling. The models make a priori assumptions that epitopes must be present only on the mature protein, solvent accessible, on the ‘top’ (peptide binding surface) of the molecule, restricted to the same class as the antibody, and in the same position on the target allele if reactive to more than one locus. Results obtained counter to these assumptions are routinely discounted. For the 17th International Histocompatibility and Immunogenetics Workshop, we developed a reverse engineering algorithm to define epitopes without these assumptions on a cohort of 332 primary transplant pairs. Complete NGS typing of the transcribed (including leader) genomic DNA for 11 HLA loci of donor and recipient and DSA assignment by single antigen beads was performed. Our results show that, when grouped by 16 class I and II allele specific DSA, uniform clusters and 172 specific amino acid target epitopes are recognized by recipients despite originating from disparate HLA pairs. Data also show that these targets can be in the leader, alpha 3, transmembrane and cytoplasmic domains, thus calling into question current assumptions regarding immunogenic epitopes. Comparisons of amino acid epitopes defined by the Terasaki and Duquesnoy groups (TerEp and EpRegistry) are given.     

Exclusion of Linkage to the HLA Region in Ninety Multiplex Sibships with Autism

Several studies have suggested a role for the histocompatibility complex of loci (HLA) in the genetic susceptibility to autism. We have tested this hypothesis by linkage analysis using genetic marker loci in the HLA region on chromosome 6p in multiplex families with autism. We have examined sharing of alleles identical by descent in 97 affected sib pairs from 90 families. Results demonstrate no deviation from the null expectation of 50% sharing of alleles in this region; in fact, for most marker loci, the observed sharing was less than 50%. Thus, it is unlikely that loci in this region contribute to the genetic etiology of autism to any significant extent in our families.