scholarly journals Use of 8-methoxypsoralen and ultraviolet-A pretreated platelet concentrates to prevent alloimmunization against class I major histocompatibility antigens

Blood ◽  
1991 ◽  
Vol 77 (11) ◽  
pp. 2530-2537 ◽  
Author(s):  
NH Grana ◽  
KJ Kao
Keyword(s):  
Class I ◽  
Major Histocompatibility ◽  
Ultraviolet A ◽  
Platelet Concentrates ◽  
Spleen Cells ◽  
Control Groups ◽  
Class I Mhc ◽  
Mhc Molecules ◽  
Major Histocompatibility Antigens ◽  
The Mean

Abstract The use of 8-methoxypsoralen (8-MOP) and UV-A irradiation to inactivate contaminating donor leukocytes in platelet concentrates and to prevent primary alloimmunization against donor class I major histocompatibility (MHC) antigens in mice was investigated. CBA/CaH-T6J mice with the H2k haplotype and BALB/cByJ mice with the H2d haplotype were used as donors and recipients, respectively. The mixed leukocyte reaction between these two strains of mice showed that treatment of spleen cells with 500 ng/mL 8-MOP and 5J/cm2 UV-A inhibited 99% of responder and 92% of stimulator function. There was no measurable loss of platelet aggregating activity after the treatment. After two weekly transfusions of platelets without any treatment, 93% of control mice (n = 15) developed anti-H2k antibody. In contrast, only 33% of mice (n = 15) receiving platelets treated with 8-MOP and UV-A became alloimmunized. After six weekly platelet transfusions, all mice became alloimmunized. Nevertheless, the mean titers of anti-H2k antibody in sera of the treated groups were significantly lower than the control groups. One hour posttransfusion recoveries of 51Cr-labeled donor platelets were also higher in mice transfused with the treated platelets. Thus, the pretreatment of platelet concentrates with 8-MOP and UV-A irradiation effectively reduced the alloantigenicity of class I MHC molecules. The implication of this finding in relation to the mechanism by which donor leukocytes allosensitize recipients is discussed.

scholarly journals Use of 8-methoxypsoralen and ultraviolet-A pretreated platelet concentrates to prevent alloimmunization against class I major histocompatibility antigens

Blood ◽  
1991 ◽  
Vol 77 (11) ◽  
pp. 2530-2537 ◽  
Author(s):  
NH Grana ◽  
KJ Kao
Keyword(s):  
Class I ◽  
Major Histocompatibility ◽  
Ultraviolet A ◽  
Platelet Concentrates ◽  
Spleen Cells ◽  
Control Groups ◽  
Class I Mhc ◽  
Mhc Molecules ◽  
Major Histocompatibility Antigens ◽  
The Mean

The use of 8-methoxypsoralen (8-MOP) and UV-A irradiation to inactivate contaminating donor leukocytes in platelet concentrates and to prevent primary alloimmunization against donor class I major histocompatibility (MHC) antigens in mice was investigated. CBA/CaH-T6J mice with the H2k haplotype and BALB/cByJ mice with the H2d haplotype were used as donors and recipients, respectively. The mixed leukocyte reaction between these two strains of mice showed that treatment of spleen cells with 500 ng/mL 8-MOP and 5J/cm2 UV-A inhibited 99% of responder and 92% of stimulator function. There was no measurable loss of platelet aggregating activity after the treatment. After two weekly transfusions of platelets without any treatment, 93% of control mice (n = 15) developed anti-H2k antibody. In contrast, only 33% of mice (n = 15) receiving platelets treated with 8-MOP and UV-A became alloimmunized. After six weekly platelet transfusions, all mice became alloimmunized. Nevertheless, the mean titers of anti-H2k antibody in sera of the treated groups were significantly lower than the control groups. One hour posttransfusion recoveries of 51Cr-labeled donor platelets were also higher in mice transfused with the treated platelets. Thus, the pretreatment of platelet concentrates with 8-MOP and UV-A irradiation effectively reduced the alloantigenicity of class I MHC molecules. The implication of this finding in relation to the mechanism by which donor leukocytes allosensitize recipients is discussed.

scholarly journals Characterization of a Murine Cytomegalovirus Class I Major Histocompatibility Complex (MHC) Homolog: Comparison to MHC Molecules and to the Human Cytomegalovirus MHC Homolog

1998 ◽  
Vol 72 (1) ◽  
pp. 460-466 ◽  
Author(s):  
Tara L. Chapman ◽  
Pamela J. Bjorkman
Keyword(s):  
Major Histocompatibility Complex ◽  
Heavy Chain ◽  
Class I ◽  
Major Histocompatibility ◽  
Class I Mhc ◽  
Endogenous Peptides ◽  
Β2 Microglobulin ◽  
Mhc Molecules ◽  
Histocompatibility Complex ◽  
Infected Cells

ABSTRACT Both human and murine cytomegaloviruses (HCMV and MCMV) down-regulate expression of conventional class I major histocompatibility complex (MHC) molecules at the surfaces of infected cells. This allows the infected cells to evade recognition by cytotoxic T cells but leaves them susceptible to natural killer cells, which lyse cells that lack class I molecules. Both HCMV and MCMV encode class I MHC heavy-chain homologs that may function in immune response evasion. We previously showed that a soluble form of the HCMV class I homolog (UL18) expressed in Chinese hamster ovary cells binds the class I MHC light-chain β2-microglobulin and a mixture of endogenous peptides (M. L. Fahnestock, J. L. Johnson, R. M. R. Feldman, J. M. Neveu, W. S. Lane, and P. J. Bjorkman, Immunity 3:583–590, 1995). Consistent with this observation, sequence comparisons suggest that UL18 contains the well-characterized groove that serves as the binding site in MHC molecules for peptides derived from endogenous and foreign proteins. By contrast, the MCMV homolog (m144) contains a substantial deletion within the counterpart of its α2 domain and might not be expected to contain a groove capable of binding peptides. We have now expressed a soluble version of m144 and verified that it forms a heavy chain–β2-microglobulin complex. By contrast to UL18 and classical class I MHC molecules, m144 does not associate with endogenous peptides yet is thermally stable. These results suggest that UL18 and m144 differ structurally and might therefore serve different functions for their respective viruses.

Antigen-induced suppression: The role of Class I major histocompatibility antigens

1985 ◽  
Vol 5 (10-11) ◽  
pp. 1007-1014 ◽  
Author(s):  
Kathryn J. Wood ◽  
Peter J. Morris
Keyword(s):  
Class I ◽  
Major Histocompatibility ◽  
Rat Erythrocytes ◽  
Histocompatibility Antigens ◽  
Class I Mhc ◽  
Specific Suppression ◽  
Mhc Antigens ◽  
Beneficial Effects ◽  
Major Histocompatibility Antigens

The role of Class I major histocompatibility (MHC) antigens in the induction of specific suppression of graft rejection has been investigated. Two experimental transplantation models have been used ’ fully vascularized heterotopic Cardiac altografts in the mouse and fully vascularized orthotopic renal allografts in the rat. Preparations of ceils expressing Class I MHC antigens, for example highly purified preparations of rat erythrocytes or platelets or mouse L cells (H2k) transfected with the D locus Class I gene of the b haplotype, LDb-1 cells, were used to pretreat recipients prior to transplantation, The function of the allograft was monitored in order to assess any beneficial effects induced by Class I MHC antigens. The results obtained implicate Class I MHC as important in the induction of specific immunosuppression of vascularized allograft rejection.

scholarly journals Ly-49 mediates EL4 lymphoma adhesion to isolated class I major histocompatibility complex molecules.

1994 ◽  
Vol 179 (3) ◽  
pp. 1011-1015 ◽  
Author(s):  
K P Kane
Keyword(s):  
Major Histocompatibility Complex ◽  
Gene Transfection ◽  
Negative Regulator ◽  
Class I ◽  
Major Histocompatibility ◽  
Cell Surface Molecule ◽  
Class I Mhc ◽  
Mhc Molecules ◽  
Histocompatibility Complex ◽  
T Lymphomas

Ly-49 is a recently identified cell surface molecule expressed on a subpopulation of natural killer (NK) cells and certain T lymphomas. It has been suggested, based on gene transfection and antibody blocking studies, that Ly-49 is a negative regulator of NK lytic activity, possibly through an interaction with target cell class I molecules. However, it has not been demonstrated that class I molecules indeed serve as ligands for Ly-49. We have found that T lymphomas expressing Ly-49 bind isolated class I major histocompatibility complex (MHC) molecules but not class II molecules immobilized on plastic. Adhesion to class I molecules was not found with T lymphomas lacking Ly-49 expression. The Ly-49 expressing EL4 lymphoma bound Dd, Dk, and Kb, but not Kd, Kk, or Db, thus demonstrating a restricted pattern of class I adhesion. The observed cell adhesion was class I density dependent, and binding to Dd and Dk was extensively inhibited by the A1 monoclonal antibody directed against Ly-49. These results provide direct evidence for Ly-49 serving as a receptor for a subset of class I MHC molecules.

scholarly journals Placental Extravillous Cytotrophoblasts Persistently Express Class I Major Histocompatibility Complex Molecules after Human Cytomegalovirus Infection

2003 ◽  
Vol 77 (15) ◽  
pp. 8187-8195 ◽  
Author(s):  
Masakazu Terauchi ◽  
Hideki Koi ◽  
Chikako Hayano ◽  
Noriko Toyama-Sorimachi ◽  
Hajime Karasuyama ◽  
...  
Keyword(s):  
Human Cytomegalovirus ◽  
Hcmv Infection ◽  
First Trimester ◽  
Class I ◽  
Type I ◽  
Major Histocompatibility ◽  
Class I Mhc ◽  
Mhc Molecules ◽  
Extravillous Cytotrophoblasts ◽  
Before And After

ABSTRACT Human cytomegalovirus (HCMV) downregulates the class I major histocompatibility complexes (MHCs), HLA-A and -B, in infected fibroblasts to escape from antigen-specific cytotoxic T lymphocytes. The HCMV genes responsible for the downregulation of MHCs are US2, US3, US6, and US11, which encode type I membrane proteins working at the endoplasmic reticulum (ER). However, it is largely unknown whether HCMV downregulates the class I MHC molecules in placental extravillous cytotrophoblasts (EVT), which express HLA-C, -E, and -G to protect a semiallogenic fetus from maternal natural killer (NK) cells at the fetomaternal interface. Here, we report that differentiated EVT prepared from human first-trimester chorionic villi persistently express class I MHC molecules upon HCMV infection. When these US proteins were expressed in uninfected EVT, they were localized at the ER in the entire cytoplasm. However, subsequent HCMV infection resulted in dissociation of these US proteins from the ER, which relocated toward the cell membrane. In fibroblasts, these US proteins were localized at the ER before and after HCMV infection. These results suggest that the US gene products are not integrated into ER of HCMV-infected EVT and fail to downregulate class I MHC molecules.

scholarly journals HHV-7 U21 exploits Golgi quality control carriers to reroute class I MHC molecules to lysosomes

2020 ◽  
Vol 31 (3) ◽  
pp. 196-208
Author(s):  
Aaron T. Dirck ◽  
Melissa L. Whyte ◽  
Amy W. Hudson
Keyword(s):  
Quality Control ◽  
Major Histocompatibility Complex ◽  
Viral Protein ◽  
Class I ◽  
Major Histocompatibility ◽  
Class I Mhc ◽  
Complex Molecules ◽  
Mhc Molecules ◽  
Histocompatibility Complex

U21 is a viral protein that forms hetero-oligomers with class I major histocompatibility complex molecules and reroutes them to lysosomes. It is shown that U21 exits from the Golgi in a distinct clathrin-independent carrier that also carries unfolded and aggregated proteins to lysosomes.

scholarly journals Human Herpesvirus 7 U21 Downregulates Classical and Nonclassical Class I Major Histocompatibility Complex Molecules from the Cell Surface

2010 ◽  
Vol 84 (8) ◽  
pp. 3738-3751 ◽  
Author(s):  
Nathan A. May ◽  
Nicole L. Glosson ◽  
Amy W. Hudson
Keyword(s):  
Major Histocompatibility Complex ◽  
Cell Surface ◽  
Infected Cell ◽  
Nk Cell ◽  
Human Herpesvirus ◽  
Class I ◽  
Major Histocompatibility ◽  
Class I Mhc ◽  
Mhc Molecules ◽  
Histocompatibility Complex

ABSTRACT Herpesviruses have evolved numerous strategies to evade detection by the immune system. Notably, most of the herpesviruses interfere with viral antigen presentation to cytotoxic T lymphocytes (CTLs) by removing class I major histocompatibility complex (MHC) molecules from the infected cell surface. Clearly, since the herpesviruses have evolved an extensive array of mechanisms to remove class I MHC molecules from the cell surface, this strategy serves them well. However, class I MHC molecules often serve as inhibitory ligands for NK cells, so viral downregulation of all class I MHC molecules should leave the infected cell open to NK cell attack. Some viruses solve this problem by selectively downregulating certain class I MHC products, leaving other class I products at the cell surface to serve as inhibitory NK cell ligands. Here, we show that human herpesvirus 7 (HHV-7) U21 binds to and downregulates all of the human class I MHC gene products, as well as the murine class I molecule H-2Kb. HHV-7-infected cells must therefore possess other means of escaping NK cell detection.

scholarly journals Presentation of Cytosolic Glycosylated Peptides by Human Class I Major Histocompatibility Complex Molecules in Vivo

1999 ◽  
Vol 190 (1) ◽  
pp. 145-150 ◽  
Author(s):  
John S. Haurum ◽  
Ingelise Bjerring Høier ◽  
Gemma Arsequell ◽  
Anne Neisig ◽  
Gregorio Valencia ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Posttranslational Modifications ◽  
Cytotoxic T Lymphocyte ◽  
Class I ◽  
Major Histocompatibility ◽  
Human Class ◽  
Class I Mhc ◽  
Mhc Molecules ◽  
Histocompatibility Complex

Antigens presented by class I major histocompatibility complex (MHC) molecules for recognition by cytotoxic T lymphocytes consist of 8–10-amino-acid-long cytosolic peptides. It is not known whether posttranslationally modified peptides are also presented by class I MHC molecules in vivo. Many different posttranslational modifications occur on cytoplasmic proteins, including a cytosolic O-β-linked glycosylation of serine and threonine residues with N-acetylglucosamine (GlcNAc). Using synthetic glycopeptides carrying the monosaccharide O-β-GlcNAc substitution on serine residues, we have shown that glycopeptides bind efficiently to class I MHC molecules and elicit a glycopeptide-specific cytotoxic T lymphocyte response in mice. In this study, we provide evidence that peptides presented by human class I MHC molecules in vivo encompass a small, significant amount of glycopeptides, constituting up to 0.1% of total peptide. Furthermore, we find that carbohydrate structures present on glycopeptides isolated from class I MHC molecules are dominated by the cytosolic O-β-GlcNAc substitution, and synthetic peptides carrying this substitution are efficiently transported by TAP (transporter associated with antigen presentation) into the endoplasmic reticulum. Thus, in addition to unmodified peptides, posttranslationally modified cytosolic peptides carrying O-β-linked GlcNAc can be presented by class I MHC molecules to the immune system.

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