Soluble HLA in human body fluids

Aultman, Donnie F.; Adamashvili, Irena; Yaturu, Kamalakar; Langford, Marlyn P.; Gelder, Frank B.; Gautreaux, Michael D.; Ghali, G.E.; McDonald, John C.

doi:10.1016/s0198-8859(98)00122-0

Cited by 34 publications

(51 citation statements)

References 38 publications

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“…sHLAs may induce apoptosis of alloreactive T cells in vitro, modulate immune responses, and play a role in the induction and maintenance of peripheral tolerance (55,56). In addition, serum levels of sHLA are increased in inflammatory and autoimmune diseases and correlate positively with disease activity and autoantibody titers (54,57), further supporting a physiological role for sHLA. In healthy individuals, serum sHLA levels vary on different HLA haplotypes (58) and in vitro, the amount of soluble DQ molecules in culture supernatants has been linked to the haplotypespecific expression of transcripts lacking DQB1 exon 4 (29).…”

Section: Discussionmentioning

confidence: 83%

“…More than 40% of alternatively spliced genes that encode single-pass transmembrane proteins produce splice variants lacking exons coding for the transmembrane domains, potentially generating soluble protein isoforms (53). Alternatively spliced HLA transcripts that lack transmembrane exons enter the endocytic compartment, are released by cells, and can be detected as soluble molecules (sHLA) in body fluids (29,54). sHLAs may induce apoptosis of alloreactive T cells in vitro, modulate immune responses, and play a role in the induction and maintenance of peripheral tolerance (55,56).…”

Section: Discussionmentioning

confidence: 99%

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Position-Dependent Repression and Promotion of DQB1 Intron 3 Splicing by GGGG Motifs

Královičová

Vořechovský

2006

The Journal of Immunology

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Alternative splicing of HLA-DQB1 exon 4 is allele-dependent and results in variable expression of soluble DQβ. We have recently shown that differential inclusion of this exon in mature transcripts is largely due to intron 3 variants in the branch point sequence (BPS) and polypyrimidine tract. To identify additional regulatory cis-elements that contribute to haplotype-specific splicing of DQB1, we systematically examined the effect of guanosine (G) repeats on intron 3 removal. We found that the GGG or GGGG repeats generally improved splicing of DQB1 intron 3, except for those that were adjacent to the 5′ splice site where they had the opposite effect. The most prominent splicing enhancement was conferred by GGGG motifs arranged in tandem upstream of the BPS. Replacement of a G-rich segment just 5′ of the BPS with a series of random sequences markedly repressed splicing, whereas substitutions of a segment further upstream that lacked the G-rich elements and had the same size did not result in comparable splicing inhibition. Systematic mutagenesis of both suprabranch guanosine quadruplets (G4) revealed a key role of central G residues in splicing enhancement, whereas cytosines in these positions had the most prominent repressive effects. Together, these results show a significant role of tandem G4NG4 structures in splicing of both complete and truncated DQB1 intron 3, support position dependency of G repeats in splicing promotion and inhibition, and identify positively and negatively acting sequences that contribute to the haplotype-specific DQB1 expression.

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Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Position-Dependent Repression and Promotion of DQB1 Intron 3 Splicing by GGGG Motifs

Královičová

Vořechovský

2006

The Journal of Immunology

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“…Few reports in the literature address inter-individual variations in saliva production, but significant differences between individuals have been described for salivary glucose clearance over time [17], for the secretion of various substances in saliva [18][19][20] as well as salivary response to stimulation by glucocorticoids [21]. Another possible explanation could rest with the patient's caffeine ingestion history, which was not included as a variable in this study.…”

Section: Discussionmentioning

confidence: 97%

Effects of Caffeine on Salivation

Barasch¹,

Gordon²

2016

Oral Health Case Reports

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“…The results presented here showed that all cell populations isolated from pregnant mice expressed IA molecules on their surface and produced soluble forms of such molecules. Soluble class II molecules have been detected in the serum, body fluids, trophoblast cell culture supernatants and are believed to have various immunoregulatory effects [34][35][36][37]. It has been suggested that soluble class II molecules isolated from mouse serum stimulate the initiation of a humoral or cellular immune response, while inhibiting the effector phase of the reactions [38].…”

Section: Discussionmentioning

confidence: 99%

Characterization of CD25‐Positive T Cells During Syngeneic Pregnancy: Production of Stimulatory Class II MHC Molecules

et al. 2009

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Various studies demonstrate that immunosuppression vis‐à‐vis paternal alloantigens may play a role for successful pregnancy. However, if this theory is true, the question that remains unanswered is how do syngeneic pregnancies manage to produce viable embryos. In allogeneic murine pregnancies immunosuppression is mediated by regulatory CD25+/Foxp3/CTLA‐4 T cells. In order to evaluate whether these cells also play a role in syngeneic pregnancies, CD25+CD4+ and CD25+CD8+ were isolated from spleens of pregnant mice and examined as to the expression of specific suppressive and stimulatory markers, cytokine and soluble MHC class II antigen production. Interestingly, the CD25+ cells and their products displayed an MHC‐restricted stimulatory activity on total spleen cell proliferation assays. Although the CD25+CD4+ and CD25+CD8+ cells expressed Foxp3, they lacked CTLA‐4, while expressing CD28. Non‐specific proliferative effect was shown to be mediated by IL‐3 and IL‐4. The MHC‐restricted proliferative effect; however, could be attributed to IAd molecules, which were detected in all culture supernatants of the T cell subpopulations tested and their elimination ablated the observed stimulatory activity. The detection of Ea, Eb1, Eb2 in addition to the Aa and Ab transcripts in these cells indicated the possible involvement of other class II gene combinations in this type of regulation. The results indicate that in the absence of paternal MHC alloantigens, maternal CD25+ cells are involved in the development of immunostimulation to ensure foetal survival.

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Soluble HLA in human body fluids

Cited by 34 publications

References 38 publications

Position-Dependent Repression and Promotion of DQB1 Intron 3 Splicing by GGGG Motifs

Position-Dependent Repression and Promotion of DQB1 Intron 3 Splicing by GGGG Motifs

Effects of Caffeine on Salivation

Characterization of CD25‐Positive T Cells During Syngeneic Pregnancy: Production of Stimulatory Class II MHC Molecules

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