bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional analysis of DR17(DR3)-restricted mycobacterial T cell epitopes reveals DR17-binding motif and enables the design of allele-specific competitor peptides.
Authors: Geluk A , Van Meijgaarden K E , Janson A A , Drijfhout J W , Meloen R H , De Vries R R , Ottenhoff T H 
Published: December 2022

Abstract
We have previously shown that p3-13 (KTIAY-DEEARR) of the 65-kDa heat shock protein (hsp65) of Mycobacterium tuberculosis and Mycobacterium leprae is selected as an important T cell epitope in HLA-DR17+ individuals, by selectively binding to (a pocket in) DR17 molecules, the major subset of the DR3 specificity. We have now further studied the interaction between p3-13, HLA-DR17 and four different TCR (V beta 5.1, V beta 1, and V beta 4) by using T cell stimulation assays, direct peptide-DR binding assays, and a large panel (n = 240) of single amino acid substitution analogs of p3-13. We find that residues 5(I) and 8(D) of p3-13 are important DR17 binding residues, whereas the residues that interact with the TCR vary slightly for each DR17-restricted clone. By using N- and C-terminal truncated derivatives of p2-20 we defined the minimal peptide length for both HLA-DR17 binding and T cell activation: the minimal peptide that bound to DR17 was seven amino acids long whereas the minimal peptide that activated T cell proliferation was eight amino acids in length. Furthermore, two new DR17-restricted epitopes were identified on hsp70 and hsp18 of M. leprae. Alignment of the critical DR17-binding residues 5(I) and 8(D) of p3-13 with these two novel epitopes and two other DR17-binding peptides revealed the presence of highly conserved amino acids at positions n and n + 3 with I, L, and V at position n and D and E at position n + 3. D and E are particularly likely to interact with the DR17-specific, positively charged pocket that we have defined earlier. Based on these results, a set of single amino acid substituted analogs that failed to activate these T cell clones but still bound specifically to DR17 was defined and tested for their ability to inhibit T cell activation by p3-13 or other DR17-restricted epitopes. Those peptides were able to inhibit the response to p3-13 as well as other DR17-restricted mycobacterial epitopes in an allele-specific manner, and are anticipated to be of potential use for immunotherapeutic and vaccine design strategies.
Characterization of gamma delta T lymphocytes at the maternal-fetal interface.
Authors: Heyborne K D , Cranfill R L , Carding S R , Born W K , O'Brien R L 
Published: December 2022

Abstract
A specific subset of gamma delta T lymphocytes bearing a V gamma 6V delta 1-encoded TCR is known to populate the normal nonpregnant murine uterine and vaginal epithelium. However, gamma delta T lymphocytes residing at the maternal-fetal interface during pregnancy have not yet been investigated. Using mAb and cytofluorographic analysis, we analyzed gamma delta TCR-bearing lymphocytes obtained from placental/decidual tissues of allogeneic (C57B1/10 X BALB/c and BALB/c X C57B1/10) pregnancies. Gestations were analyzed at several time points during the second half of pregnancy, with lymphocytes from both maternal spleen and nonpregnant C57B1/10 uteri analyzed as controls. We found that all gamma delta T lymphocytes at the maternal-fetal interface are maternally derived. Relative to the total T lymphocyte population, the percentage of gamma delta TCR-bearing T lymphocytes at the maternal-fetal interface is enriched three- to four-fold compared with maternal spleen, and twofold compared with nonpregnant uteri. Although one-third of gamma delta T lymphocytes from pregnant animals express a cell-surface marker associated with activation (IL-2R), gamma delta cells from uteri of nonpregnant mice fail to express IL-2R. In terms of absolute numbers, we estimate that reproductive-tract gamma delta T cells are increased nearly 100-fold in pregnant animals compared with nonpregnant animals. To characterize the TCR-gamma delta repertoire in the placenta/decidua, we generated 21 TCR-gamma delta-bearing hybridomas from lymphocytes in this tissue. Analysis of these hybridomas revealed at least six distinct gamma delta receptor types expressed at the maternal-fetal interface, with V gamma 6V delta 1 encoded TCR representing the predominant population. As specific resident constituents of the reproductive tract, gamma delta T lymphocytes may be involved in regulating a variety of physiologic and pathophysiologic events in reproductive biology.
C33 antigen recognized by monoclonal antibodies inhibitory to human T cell leukemia virus type 1-induced syncytium formation is a member of a new family of transmembrane proteins including CD9, CD37, CD53, and CD63.
Authors: Imai T , Fukudome K , Takagi S , Nagira M , Furuse M , Fukuhara N , Nishimura M , Hinuma Y , Yoshie O 
Published: December 2022

Abstract
C33 Ag was originally identified by mAb inhibitory to syncytium formation induced by human T cell leukemia virus type 1. The Ag was shown to be a highly heterogeneous glycoprotein consisting of a 28-kDa protein and N-linked oligosaccharides ranging from 10 to 50 kDa. In the present study, cDNA clones were isolated from a human T cell cDNA expression library in Escherichia coli by using mAb C33. The identity of cDNA was verified by immunostaining and immunoprecipitation of transfected NIH3T3 cells with mAb. The cDNA contained an open reading frame of a 267-amino acid sequence which was a type III integral membrane protein of 29.6 kDa with four putative transmembrane domains and three putative N-glycosylation sites. The C33 gene was found to belong to a newly defined family of genes for membrane proteins, such as CD9, CD37, CD53, CD63, and TAPA-1, and was identical to R2, a cDNA recently isolated because of its strong up-regulation after T cell activation. Availability of mAb for C33 Ag enabled us to define its distribution in human leukocytes. C33 Ag was expressed in CD4+ T cells, CD19+ B cells, CD14+ monocytes, and CD16+ granulocytes. Its expression was low in CD8+ T cells and mostly negative in CD16+ NK cells. PHA stimulation enhanced the expression of C33 Ag in CD4+ T cells by about 5-fold and in CD8+ T cells by about 20-fold. PHA stimulation also induced the dramatic size changes in the N-linked sugars previously shown to accompany human T cell leukemia virus type 1-induced transformation of CD4+ T cells.
Long term expression of IL-4 in vivo using retroviral-mediated gene transfer.
Authors: Chambers C A , Kang J , Hozumi N 
Published: December 2022

Abstract
Th cell subsets regulate immune responses by cell-cell interaction and secretion of cytokines. IL-4 is one of the cytokines secreted by Th cells important for cellular and humoral, particularly IgG1 and IgE responses. To study the role of IL-4 in T cell development and regulation of immune responses in vivo, low IgE-responder C57BL/6 mice were reconstituted with bone marrow cells that had been infected with recombinant retrovirus expressing a high level of IL-4. The reconstituted mice expressed retroviral IL-4 transcripts (9/10) even 8 mo postreconstitution. Physiologically significant levels of IL-4 were detected in the majority of the provirus-positive animals tested (5/8). Ectopic expression of exogenous IL-4 in hematopoietic cells had dramatic effects on T cell development resulting in changes in CD4:CD8 ratios. Moreover, the levels of serum IgG1 and, with antigenic stimulation, IgE were also increased. These results demonstrate that the retrovirus gene transfer system can be used to study the effects of ectopic cytokine gene expression in vivo on Ig isotype regulation and T helper cell subset differentiation.
The HLA-E gene encodes two differentially regulated transcripts and a cell surface protein.
Authors: Ulbrecht M , Honka T , Person S , Johnson J P , Weiss E H 
Published: December 2022

Abstract
An HLA-E-specific oligonucleotide probe was used to study the expression of HLA-E. This probe detects two HLA-E transcripts, 1.8 and 2.7 kb in size, which are present in varying ratios in all tissues and cell lines investigated. We demonstrate that alternative poly(A) site usage accounts for the differential regulation of the two HLA-E mRNA species. Sequence analysis of three cDNA clones, representing the two transcripts of HLA-E, and of an HLA-E gene encoded by cosmid cd3.14, revealed identity of gene and cDNA in the 3' untranslated region. S1 nuclease protection assays confirmed that the two HLA-E transcripts are not alternative splicing products. Introduction of cd3.14, together with human beta 2 m into the murine myeloma cell line P3X63-Ag8.653, resulted in a cell surface expression of an HLA-class I heavy chain detectable by indirect immunofluorescence whereas transfection into the human beta 2m expressing mouse L cell line, J27 was negative with regard to cell surface expression. Cell surface labeling of transfectants and immunoprecipitation with a monomorphic HLA class I-specific antibody or an antibody against human beta 2m confirmed the presence of an HLA-E H chain on the cell surface. These results indicate that the HLA-E gene codes for a class I H chain that can be expressed on the cell surface.
Regulation of IL-2 receptor subunit genes in human monocytes. Differential effects of IL-2 and IFN-gamma.
Authors: Espinoza-Delgado I , Longo D L , Gusella G L , Varesio L 
Published: December 2022

Abstract
We investigated the effects of IFN-gamma and IL-2 on IL-2R alpha and beta mRNA expression in human monocytes. Low basal expression of IL-2R beta mRNA was detected in fresh monocytes. Stimulation of monocytes with IL-2 induced a significant increase of IL-2R beta mRNA, but did not induce IL-2R alpha mRNA. In contrast, stimulation of monocytes with IFN-gamma-induced IL-2R alpha mRNA, but did not modify IL-2R beta mRNA. Five U/ml of IFN-gamma induced IL-2R alpha mRNA and 2.2 nM of IL-2 induced IL-2R beta mRNA, both within 3 h. Nuclear run-on experiments demonstrated that the induction of IL-2R alpha mRNA by IFN-gamma is controlled, at least in part, at the transcriptional level. In contrast, the enhancement of IL-2R beta mRNA by IL-2 is controlled at a posttranscriptional level and is associated with an increase in the half-life of IL-2R beta mRNA. The results of studies on the cytotoxic activity and on the expression of c-fms mRNA of monocytes activated by the combination of IFN-gamma and IL-2 show that pretreatment with IFN-gamma renders monocytes more sensitive to activation by IL-2. These results demonstrate that the IL-2R alpha and IL-2R beta subunits are induced by different lymphokines through distinct mechanisms and that both receptor subunits can influence the response of monocytes to IL-2.
Kinetic analysis of cytokine gene expression in the livers of naive and immune mice infected with Listeria monocytogenes. The immediate early phase in innate resistance and acquired immunity.
Authors: Ehlers S , Mielke M E , Blankenstein T , Hahn H 
Published: December 2022

Abstract
The anamnestic response to infection with Listeria monocytogenes is characterized by the rapid elimination of normally lethal doses of bacteria and accelerated granuloma formation. These phenomena are mediated by listeria-specific memory T cells within the first 24 h after reinfection. In order to elucidate the mechanisms operative during this decisive phase of infection, we conducted a comprehensive kinetic and quantitative analysis of cytokine gene expression in the livers of naive and immune mice. Organs were removed at 30 min, and 1, 2, 6, and 24 h after primary and secondary infections, and PCR3-assisted messenger RNA (mRNA) amplification was performed on matched samples using primers specific for IL-1 beta, IL-6, M-CSF, GM-CSF, TNF-alpha, IFN-gamma, IL-10, IL-4, IL-2, IL-3 and I1-2Rp55. The cytokine pattern characteristic of secondarily infected animals differed qualitatively by the expression of mRNA for IL-2, IL-2Rp55, IL-3, and IL-4, demonstrating the accumulation and activation of specific T cells in the livers as early as 1 to 2 h after reinfection. Combined in vivo depletion of both CD4+ and CD8+ T cells before reinfection almost completely abrogated the differentiated cytokine profile typical of the anamnestic response. Using competitive PCR for semiquantitative determination of mRNA levels, the amount of IL-1 beta and IL-6 mRNA was found to be very similar during primary and secondary infection, whereas TNF-alpha mRNA was found to be increased by approximately 10-fold 2 h and IFN-gamma mRNA by approximately 50 to 100-fold 6 h after reinfection when compared with a primary challenge. Combined in vivo depletion of both CD4+ and CD8+ T cells before reinfection resulted in a substantial (approximately 10-fold) decrease in IFN-gamma mRNA expression. To correlate these findings with cytokine secretion, spleen cells from naive and immune as well as normal and CD4+ and CD8+ cell depleted mice infected 6 h previously were cultured for 48 h, and supernatants were analyzed for the amount of the above mentioned cytokines. Semiquantitative PCR-assisted mRNA amplification is demonstrated to be a superior tool in dissociating the mediators of innate resistance from those operative in protective immunity and granuloma formation.
Studies in Specific Hypersensitiveness
Authors: Coca A. F. , Milford E. L. 
Published: December 2022

Abstract
House Dust Extract The use of house dust extract has been limited by the weak concentration of the specific excitant in the fluid extract. Even when the extracting fluid was used in a quantity just sufficient to wet the dust, the extracts were active in the intradermal test in a dilution of at most 1:10, and they were never capable of causing a diagnostic cutaneous reaction with the scratch method.
We have endeavored to concentrate the extract after dialysis against buffered saline solution by evaporation with the use of an electric fan, without heating, and by evaporation in vacuo at 37°C., with the aid of a current of nitrogen gas. Neither of these procedures accomplished a concentration of the activity of the extract. No such concentrated preparation was found capable of causing a diagnostic cutaneous reaction with the scratch technic.
Anaphylaxis
Authors: Elmore Mary E. 
Published: December 2022

Abstract
This work is a continuation of a study of the antigenic properties of these organisms previously reported (1). The forms used were Euglena gracilis, Stichococcus sp., Chlamydomonas sp., and two species of Chlorella. In spite of the low agglutinin and precipitin titers obtained, experiments were carried out to determine whether it might be possible to sensitize guinea pigs to these organisms, either actively with a protein extract, or passively with the serum of the treated rabbits.
The Dale test was carried out with 33 virgin guinea pigs. Table 1 summarizes the results with certain of these selected to report upon here.
In the case of active sensitization to Euglena gracilis clearly positive reactions were obtained with the majority of living horns. Immune rabbit serum with a sedimentation titer as previously described did not passively sensitize. With the other antigens ten to twelve daily injections were necessary for sensitization.
Anaphylaxis
Authors: Sherwood Noble P. , Downs C. M. 
Published: December 2022

Summary and Conclusions
Passive sensitization of turtles was accomplished by injecting them with some of the high titered immune rooster serum used to passively sensitize chick embryos. The reaction was specific and similar to that in the chick embryo. It consisted in a marked slowing of the heart, increase in distole and a decrease in amplitude and a sinking of the heart to a lower level. There was an apparent rise in tone probably due to the latter phenomenon. In 2 turtles that showed positive results for passive sensitization, the hearts survived eighteen hours with regular rhythms. Sensitivity had not returned during this time. Reversed anaphylaxis was not demonstrated in 7 turtles and a doubtful positive was obtained in 1. The incubation period for the latter was two hours. The shortest incubation period for passive sensitization was four hours while the average was twenty-four to forty-eight hours. High titered immune serum from rabbits failed to passively sensitize in a short series of 16 turtles.
Parenteral Denaturization of Foreign Proteins
Authors: Manwaring W. H. , Marino H. D. , Azevedo J. L. 
Published: December 2022

Summary
Titrations by means of rabbit precipitin indicate that horse proteins injected intravenously into normal dogs are retained apparently quantitatively in the circulation for at least ten days. Nevertheless, transfusions from these dogs into partially exsanguinated normal recipients show that these proteins are so altered by the seventh day as almost completely to lose their specific sensitizing power.
It is conceivable that this parenteral denaturization is an initial stage in specific antibody formation.
Bacteriophage and Phagocytosis
Authors: Smith George H. 
Published: December 2022

Abstract
Of the many phenomena which appear to be initiated or, at least, intensified through the action of bacteriophage that of bacterial dissolution has received by far the greatest amount of attention. This is but natural since the process of bacterial dissolution through this agent is by far the most spectacular manifestation of its activity. It does not necessarily follow, from either the biological point of view or from the standpoint of immunology, that this manifestation of bacteriophage is the most significant.
The rôle of the bacteriophage in inciting or in accelerating microbic dissociation may, perhaps, be a matter of far greater biological import than is actual bacterial dissolution, and from the standpoint of immunology it may very well be that, under certain circumstances at least, the influence of bacteriophage upon phagocytosis may be far more significant than is the direct action of bacteriophage upon the bacterial cell.
The Immunological Significance of the Tuberculous Tissue
Authors: Dienes L. 
Published: December 2022

Summary
The introduction of antigens directly into the tuberculous lesions incites more antibody production than the subcutaneous and intravenous treatment of the tuberculous animal. Under appropriate conditions only the injection of the antigens in the tuberculous lesions is effective.
It is very probable that the antibodies are formed in the tuberculous tissue and that the formation of the pathological tissue is the cause of the increased antibody production after tuberculous infection.
The Effect of Chloroform on the Immunizing Action of Vaccine Virus
Authors: Duran-Reynals F. 
Published: December 2022

Summary and Conclusions
When vaccine virus was so far inactivated by chloroform that no eruption resulted from the intradermal injection of very large doses, no immunity was induced in the animals.
When the chloroform virus produced any lesion whatever, the rabbits subsequently proved immune when tested by a second injection of untreated virus.
These experiments support the general idea that inactivated vaccine virus is incapable of giving rise to immunity.
Some Causes of Variation in the Laboratory Interpretation of Complement Fixation by Different Methods
Authors: Wilson M. A. , Forbes Mary V. , Nedley Rose M. , Honig Florence 
Published: December 2022

Abstract
The observations reported in this paper have been emphasized by their recurrence in several studies of the complement fixation test in which we had the coöperation of other laboratories.
In 1922 we made a study of the Kolmer (1) (2) standard method for complement fixation test as an aid to the diagnosis of syphilis, in coöperation with the laboratories of New York University and of New York Hospital. We had difficulty in drawing conclusions from those comparison tests because of the different criteria for interpretation of the two methods employed by the coöperating laboratories.
In 1925 we participated in the work of the American Public Health Association Committee on Standardization of the Wassermann Test. Here, again, we had to take into consideration various criteria for interpretation before an accurate comparison could be made of the tests by the different laboratories.
Functional consequences of engagement of the T cell receptor by low affinity ligands.
Authors: Alexander J , Snoke K , Ruppert J , Sidney J , Wall M , Southwood S , Oseroff C , Arrhenius T , Gaeta F C , Colón S M 
Published: December 2022

Abstract
The mechanisms involved in TCR antagonism by Ag analog/MHC have been analyzed. A detailed structure-activity relationship study indicated that modification of any of the major T cell contact residues of the peptide molecule can yield a powerful antagonist. It was also shown that as the analog structure increased in similarity to the Ag, the capacity to antagonize Ag-TCR interaction increased up to the point that the analogs themselves became antigenic. These data strongly suggest an affinity-related mechanism whereby a certain affinity is required for signaling through the TCR, and that below this level there can be sufficient affinity to engage the receptor such that triggering does not occur and antagonism can be detected. Taking advantage of this information, antagonist peptides active down to the 10 nM range were engineered. Thus, this approach demonstrates for the first time a rational approach to designing effective, selective low m.w. compounds with high potential in treatment of allergies and autoimmune diseases.
T cell antigen receptor-eta subunit. Low levels of expression and limited cross-species conservation.
Authors: Jensen J P , Cenciarelli C , Hou D , Rellahan B L , Dean M , Weissman A M 
Published: December 2022

Abstract
The eta-subunit of the TCR is derived from an alternative splice product of the TCR-zeta gene. The eta-subunit has been extensively characterized in murine T cells, where up to 10% of TCR bear zeta-eta heterodimers rather than zeta-homodimers. In contrast to the significant levels of eta found in murine T cells, in human PBL an eta-like region is expressed spliced to upstream exons of the zeta-gene at no more than 0.25% the level of zeta-mRNA. Analysis of genomic DNA from five additional mammalian species demonstrated that eta-like sequences are highly conserved at a nucleic acid level. The protein sequences encoded in the eta-regions from various species ranged from 28 to 92 amino acids in length, with the first seven deduced amino acids of eta-being common to all species. Within three to five amino acids of this region, all species have five consecutive charged amino acids. Beyond this point, due to translation in different reading frames, there is no significant amino acid homology. The findings of low level of expression of eta-RNA, limited cross-species conservation on a protein level, and the lack of an established functional role for this alternative splice product raise questions as to the potential roles that this subunit may play in TCR function.
Effector functions of a mouse IgG that lacks the entire CH1 domain. C1q binding and complement fixation in the absence of antigen.
Authors: Mizutani R , Igarashi T , Tanaka T , Shimada I , Arata Y 
Published: December 2022

Abstract
C1q binding and complement fixation were examined of a short-chain IgG2a antibody that lacks the entire CH1 domain. This short-chain antibody has been reported to have a low level of constitutive complement-activating activity in the absence of Ag. Two-dimensional SDS/PAGE and cation-exchange chromatography have demonstrated that two types of IgG2a proteins are secreted by the short-chain IgG2a antibody producing cell line. It has been shown that 1) the difference between these two types of the IgG2a proteins is whether the two L chains are linked by a disulfide bridge or not, and 2) C1q-binding and complement-activating activities are expressed only when the inter L chain disulfide bridge does not exist. A molecular model is presented for the active form of the short-chain IgG2a antibody.