HLA expression on immature and mature human germ cells

Hutter, Heinz; Dohr, Gottfried

doi:10.1016/s0165-0378(98)00032-1

Cited by 68 publications

(70 citation statements)

References 79 publications

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“…In our studies with the rhesus, whereas there was only very rarely detectable membrane-bound Mamu-AG within the seminiferous tubules (as determined by 25D3 staining), it was clear that abundant soluble protein was present in selected germ cell populations, colocalized with Mamu-AG mRNA. The lack of ␤ 2 -microglobulin within the rhesus seminiferous tubules sufficiently explains the lack of cell surface protein, an observation made previously with the human testis and the pan-MHC class I Ab W6/32 (43). Free class I H chain was detected in some spermatocyte populations in humans (43).…”

Section: Discussionsupporting

confidence: 56%

“…The lack of ␤ 2 -microglobulin within the rhesus seminiferous tubules sufficiently explains the lack of cell surface protein, an observation made previously with the human testis and the pan-MHC class I Ab W6/32 (43). Free class I H chain was detected in some spermatocyte populations in humans (43). However, it seems unlikely that testicular soluble HLA-G may be the source of circulating serum HLA-G in men, since the patency of the blood-testis barrier would preclude this route of trafficking of the molecule.…”

Section: Discussionsupporting

confidence: 56%

“…The pattern of soluble MHC class I expression in the rhesus testis was unexpected. HLA-G protein was not detected in human testes in previous studies (5,41), although mRNA expression has been reported in some, but not all, studies (42,43). In our studies with the rhesus, whereas there was only very rarely detectable membrane-bound Mamu-AG within the seminiferous tubules (as determined by 25D3 staining), it was clear that abundant soluble protein was present in selected germ cell populations, colocalized with Mamu-AG mRNA.…”

Section: Discussioncontrasting

confidence: 55%

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A Soluble Isoform of the Rhesus Monkey Nonclassical MHC Class I Molecule Mamu-AG Is Expressed in the Placenta and the Testis

Ryan¹,

Grendell²,

Geraghty

et al. 2002

The Journal of Immunology

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The nonclassical MHC class I locus HLA-G is expressed primarily in the placenta, although other sites of expression have been noted in normal and pathological situations. In addition, soluble HLA-G isoforms have been detected in the serum of pregnant and nonpregnant women as well as men. The rhesus monkey placenta expresses a novel nonclassical MHC class I molecule Mamu-AG, which has features remarkably similar to those of HLA-G. We determined that the rhesus placenta expresses Mamu-AG mRNA (Mamu-AG5), retaining intron 4 as previously noted in HLA-G5. Immunostaining experiments with Ab 16G1 against the soluble HLA-G5 intron 4 peptide demonstrated that an immunoreactive protein(s) was present in the syncytiotrophoblasts of the chorionic villi of the rhesus placenta, within villous cytotrophoblasts, and occasionally within cells of the villous stroma. The Mamu-AG5 mRNA was readily detected in rhesus testis (although not in ejaculated sperm). Whereas an Ab against membrane-bound Mamu-AG stained few cells, primarily in the interstitium of the testis, there was consistent immunostaining for Mamu-AG5 in cells within the seminiferous tubules, which was corroborated by localization of Mamu-AG mRNA by in situ hybridization. While primary spermatocytes were negative, Sertoli cells, spermatocytes, and spermatids were consistently positive for 16G1 immunostaining. The specific recognition of the soluble Mamu-AG isoform was confirmed by Western blotting of Mamu-AG5 expressed in heterologous cells. The results demonstrate that a soluble nonclassical MHC class I molecule is expressed in the rhesus monkey placenta and testis, and confirm and extend the unique homology between HLA-G and the rhesus nonclassical molecule Mamu-AG.

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Section: Discussionsupporting

confidence: 56%

Section: Discussionsupporting

confidence: 56%

Section: Discussioncontrasting

confidence: 55%

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A Soluble Isoform of the Rhesus Monkey Nonclassical MHC Class I Molecule Mamu-AG Is Expressed in the Placenta and the Testis

Ryan¹,

Grendell²,

Geraghty

et al. 2002

The Journal of Immunology

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“…Mouse sperm has been shown to express both class I and class II MHC [74], as well as H-Y [75], all of which have the potential to interact with reactive lymphocytes, and are commonly expressed by the conceptus. In the case of human sperm, it remains controversial whether MHC antigens are expressed on the sperm surface [76][77][78]. However, it is evident that a number of leukocytes and epithelial cells are also present in the ejaculate, and these have been shown to express MHC antigens [73].…”

Section: Antigenic Characteristics Of Semenmentioning

confidence: 99%

Seminal fluid and reproduction: much more than previously thought

Bromfield

2014

J Assist Reprod Genet

127

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The influence of seminal plasma on the cytokine and immune uterine environment is well characterised in mice and humans, while the effects of disruption to uterine seminal plasma exposure on pregnancy and offspring health is becoming more clearly understood. The cellular and molecular environment of the uterus during the pre-and peri-implantation period of early pregnancy is critical for implantation success and optimal foetal and placental development. Perturbations to this environment not only have consequences for the success of pregnancy and neonatal health and viability, but can also drive adverse health outcomes in the offspring after birth, particularly the development of metabolic disorders such as obesity, hypertension and insulin resistance. It is now reported that an absence of seminal plasma at conception in mice promotes increased fat accumulation, altered metabolism and hypertension in offspring. The evidence reviewed here demonstrates that seminal plasma is not simply a transport medium for sperm, but acts also as a key regulator of the female tract environment providing optimal support for the developing embryo and benefiting future health of offspring.

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“…Restriction of CT antigen expression to immunoprivileged normal tissues (Head and Billingham, 1985;Hutter and Dohr, 1998) and high-frequency expression in different types of cancer make them attractive candidates for cancer-specific immunotherapy (Scanlan et al, 2002). A large number of CT antigens can be clustered into families containing multiple homologous members (e.g.…”

mentioning

confidence: 99%

Restriction of GAGE protein expression to subpopulations of cancer cells is independent of genotype and may limit the use of GAGE proteins as targets for cancer immunotherapy

et al. 2006

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The GAGE cancer testis antigen gene family encodes products that can be recognized by autologous T cells, and GAGE proteins have been suggested as potential targets for cancer immunotherapy. Analysis of GAGE expression in tumours has primarily been performed at the level of gene transcription, whereas little is known about GAGE expression at the protein level. To evaluate the potential of GAGE proteins as targets for cancer-specific immunotherapy, we studied the expression of these proteins in normal and malignant cells/tissues using a novel panel of monoclonal antibodies. Immunohistochemical analysis of more than 250 cancer specimens demonstrated that GAGE proteins were frequently expressed in numerous cancer types and correlated with the expression of the cancer testis antigens MAGE-A1 and NY-ESO-1. Significant intercellular and subcellular differences in GAGE protein levels were observed, and most GAGE-positive tumours also contained cancer cells lacking GAGE expression. Studies of genetically homogenous cell lines with similar intercellular heterogeneous GAGE expression showed that GAGE expression was not associated with a specific genotype, but defined a phenotypically distinct population of cells. Surprisingly, in normal tissues we found that GAGE proteins were not restricted to testis, but were also present in a subset of oocytes of resting primordial follicles and in maturing oocytes. This is the first time that a cancer testis antigen has been reported in postfoetal oocytes. The lack of GAGE expression in a subset of cancer cells within GAGE-positive tumours has decisive implications for the development of GAGE-targeted cancer therapy.

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HLA expression on immature and mature human germ cells

Cited by 68 publications

References 79 publications

A Soluble Isoform of the Rhesus Monkey Nonclassical MHC Class I Molecule Mamu-AG Is Expressed in the Placenta and the Testis

A Soluble Isoform of the Rhesus Monkey Nonclassical MHC Class I Molecule Mamu-AG Is Expressed in the Placenta and the Testis

Seminal fluid and reproduction: much more than previously thought

Restriction of GAGE protein expression to subpopulations of cancer cells is independent of genotype and may limit the use of GAGE proteins as targets for cancer immunotherapy

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