The study of the HLA system was primarily initiated to understand the basis for the histocompatibility between recipients and tissue donors. HLA typing methods are being continuously improved and biochemical and molecular typing, in particular, are expected to provide precise typing of the HLA system. Conventional HLA typing methods can define antigen specificities, while biochemical and molecular methods will provide direct allele typing that is based on the actual sequence polymorphism. The precise tissue typing will definitely improve the outcome of transplantation. Structural studies have revealed the highly polymorphic nature of the HLA system and given insight to understanding the molecular basis of the HLA polymorphism. One big immunological puzzle remaining to be answered is how T-cell receptor molecules recognize peptide antigen in conjunction with the HLA molecule. The crystallization of the T-cell receptor molecule, an experiment currently underway, will eventually reveal the structural basis of the trimolecular interaction.
Animals ; Genes, MHC Class I ; Genes, MHC Class II ; Histocompatibility Antigens Class I/analysis/chemistry/*physiology ; Histocompatibility Antigens Class II/analysis/chemistry/*physiology ; Human ; Polymorphism (Genetics) ; Protein Conformation

No abstract available.
Animal ; Antigens, Viral/genetics ; Cytokines/genetics ; Genes, MHC Class II ; Immune Tolerance ; Mice ; Mice, Transgenic ; Receptors, Antigen, T-Cell/genetics

OBJECTIVETo investigate the association of HLA class I and II alleles with generalized vitiligo in ethnic Han Chinese in north China.

METHODSBy employing polymerase chain reaction sequence-specific primer (PCR-SSP) procedure 34 generalized vitiligo patients in north China were studied for HLA I and II alleles and were compared with 102 healthy controls.

RESULTSThe allelic frequencies of HLA-A*30, Cw*06, DRB1*07, and DQB1*0201 were increased significantly in generalized vitiligo and especially in the patients without family history compared with the controls.

CONCLUSIONThese alleles positively associated with generalized vitiligo in Chinese Han patients in north China, might provide clues to reveal the susceptibility gene(s) of vitiligo in Chinese and as well as the immunnogenetic mechanisms of disease.

Adult ; Aged ; Aged, 80 and over ; Alleles ; Asian Continental Ancestry Group ; genetics ; China ; Female ; Gene Frequency ; Genes, MHC Class I ; genetics ; Genes, MHC Class II ; genetics ; Genotype ; Humans ; Male ; Middle Aged ; Vitiligo ; ethnology ; genetics

The expression of a soluble protein on cell surface is often desirable for study of a functional protein, wide application of a protein or investigation of protein-protein interaction. The expression of a soluble protein on the surface of a cell is often achieved by genetically linking a protein to the extra-cellular fragment of a transmembrane partner. In this study, the myc epitope was linked with N terminal of transmembrane proteins either A2TM or deltaLNGFR amplified by overlapping PCR. The plasmids expressing fusion protein were transfected into 293FT cells and the expression of target proteins was evaluated by fluorescent microscope, flow cytometry and Western blotting. The results of flow cytometry revealed that both A2TM and deltaLNGFR were expressed on the cell surface, but A2TM could only be detected with high copy number. Western blotting showed that the expression level of deltaLNGFR was very high and protein was heavily glycosylated, by contrast the expression of A2TM was hardly detected. The results indicate that glycosylated deltaLNGFR is a good candidate partner for the expression of a soluble protein on the cell surface.
Apoptosis Regulatory Proteins ; biosynthesis ; genetics ; Cell Membrane ; metabolism ; Genes, MHC Class II ; genetics ; HLA-A2 Antigen ; biosynthesis ; genetics ; Humans ; Membrane Fusion Proteins ; genetics ; metabolism ; Membrane Proteins ; genetics ; metabolism ; Proto-Oncogene Proteins c-myc ; metabolism

Moyamoya disease is characterized by progressive cerebrovascular occlusion at the peripheral internal carotid artery and development of abnormal collateral circulation at the cerebral basal region. Although abnormal thrombogenesis, inflammation and autoimmune process might be involved in the etiology, the genetic pathogenesis of Moyamoya disease is still unknown. To evaluate the association of Moyamoya disease with HLA alleles in the Korean population, we investigated HLA class I and class II alleles in 28 Moyamoya patients and 198 unrelated healthy controls. The frequency of HLA-B35 allele was significantly increased in the patients compared to the controls (32.1% vs. 10.1%, RR=4.2, p<0.008). Further analysis of HLA-B35 on onset age and sex showed that this allele was significantly increased compared to the controls in both late-onset and female group. Especially, HLA-B35 was the most significantly increased in female of late-onset group compared to the controls. These results suggest that HLA-B35 may be an useful genetic marker for Moyamoya disease, and particularly in females of late onset group in the Korean population.
Adolescent ; Adult ; Age of Onset ; Aged ; Child ; Child, Preschool ; Female ; Gene Frequency ; *Genes, MHC Class I ; *Genes, MHC Class II ; Genetic Markers ; Genetic Predisposition to Disease ; Genotype ; HLA Antigens/*genetics ; Human ; Korea ; Male ; Middle Aged ; Moyamoya Disease/*genetics/*immunology ; Retrospective Studies ; Support, Non-U.S. Gov't

The work was done to study immunogenetic peculiarities of neuroinflammatory diseases among Korean children. A total of 13 children with neuroinflammatory diseases (8 males and 5 females; mean age 4.6+/-2.6 yr) were consecutively recruited. Genomic typing was performed on their HLA DRB/HLA DQB genes using PCR-SSOP/ SSP techniques with gel immunoelectrophoresis. The frequencies of HLA-DR1* 15 in children with acute disseminated encephalomyelitis (ADEM) (31%) and DQB1* 06 in other neuroinflammatory diseases (38%) were significantly increased compared with control subjects. The frequencies of HLA-DRB3*0202 (100%), HLA-DRB1*1302 (67%), HLA-DRB3*0301 (67%), and HLA-DQB1*0301 (67%) were significantly increased in children with multiple sclerosis and the frequencies of HLA-DRB1*1501 (40%) and HLA-DRB5*0101 (40%) were significantly increased in children with ADEM. HLA-DRB1*1401, HLA- DRB3*0202, and HLA-DQB1*0502 were found in children with acute necrotizing encephalopathy. In conclusion, HLA-DR1*15 and DQB1*06 may be involved in susceptibility to inflammation in Korean children. The frequencies of HLA-DRB1*1501, HLA-DRB5*0101, HLA-DRB3*0301, and HLADQB1* 0602 were not as high in Korean children with multiple sclerosis as in western children. However, HLA-DRB3*0202 was seen in all children with multiple sclerosis. Our data may provide further evidence that the immunogenetic background of neuroinflammatory diseases in Korean is distinctly different from the ones in western countries. Further studies are necessary to confirm this finding.
Alleles ; Child ; Child, Preschool ; Electrophoresis ; Encephalomyelitis/genetics ; Female ; Genes, MHC Class II/*genetics ; *Genetic Predisposition to Disease ; Genotype ; Human ; Inflammation/*genetics ; Male ; Multiple Sclerosis/genetics ; Neurons/*pathology ; Polymerase Chain Reaction ; Polymorphism, Single-Stranded Conformational ; Support, Non-U.S. Gov't

It has been speculated that human leukocyte antigen (HLA) alleles are associated with the outcome of hepatitis B virus (HBV) infection although the data obtained from various populations have shown some inconsistencies. A total of 464 HBVinfected Korean individuals (80 spontaneously recovered [SR] and 384 chronically infected [CI]) were selected to investigate the association of HLA class II alleles with the viral clearance and persistence. Our results showed that: 1) multiple HLA class II alleles and haplotypes were associated with viral clearance (DRB1*1302, DRB1*1502, DQB1*0302, DQB1*0609, and related-haplotypes) and persistence (DRB1*0701, DQB1*0301, and related-haplotypes); 2) DRB1*1302 and DQB1* 0609 were more strongly associated with viral clearance. And the association of DQB1*0609 (pc=0.0084; OR, 7.24) with vial clearance was much stronger than previously recognized, DRB1*1302 (pc=0.0038; OR, 4.34); and 3) linkage to a specific DPB1 allele in a haplotype strengthened the association with viral clearance, although DPB1 itself was not associated with the outcome. These results indicate the existence of multiple factors controlling viral clearance in the HLA class II gene region. Further extended investigation on the genetic factors related to the outcome of HBV infection will provide valuable insights into the understanding of the mechanisms involved.
Alleles ; *Genes, MHC Class II ; HLA Antigens/*genetics ; HLA-DQ Antigens/*genetics ; HLA-DR Antigens/*genetics ; *Haplotypes ; Hepatitis B/*immunology/*virology ; Hepatitis B virus/genetics ; Humans ; Immunophenotyping ; Korea ; Models, Genetic ; Remission Induction ; Treatment Outcome

The role of MHC class II transactivator (C II TA) in constitutive or IFN-gamma inducible expression of HLA molecules in human malignant hematological cell lines was investigated. The expression of HLA molecules and C II TA protein was detected by Western blot, immunohistochemistry and flow cytometry. The expression of C II TA gene was determined by RT-PCR. The capability of peripheral blood T cell reaction stimulated by tumor cells was monitored by mixed lymphocyte reaction. It was found that the HLAII-positive tumor cells expressed the C II TA quite well, and the expression of HLA I + II was increased in the tumor cells with constitutive or inducible expression of C II TA after induced by IFN-gamma. The tumor cells which did not express C II TA after induced by IFN-gamma were not response to the expression of HLA II promoted by IFN-gamma. It suggests a correlation between the inability of some malignant hematological cell lines in response to IFN-gamma for HLA expression and the deficiency in the inducible expression of C II TA, indicating C II TA might take part in the regulation of HLA I + II expression in the tumor cells, which might play an important role in tumor immunologic escape.
Animals ; Genes, MHC Class II ; genetics ; HL-60 Cells ; HLA Antigens ; biosynthesis ; genetics ; Humans ; Interferon-gamma ; pharmacology ; K562 Cells ; Leukemia ; metabolism ; pathology ; Nuclear Proteins ; biosynthesis ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Trans-Activators ; biosynthesis ; genetics ; U937 Cells

OBJECTIVETo investigate the role of MHC class II Transactivator (C II TA) in expression of HLA molecules in five human malignant hematological cell lines.

METHODSThe expressions of HLA molecules and C II TA protein were detected by immunohistochemistry and flow cytometry. The expression of C II TA gene was detected by RT-PCR. The response of peripheral T cells after stimulation by Jurkat cells was detected by mixed lymphocyte reaction.

RESULTThe HLA II-positive tumor cells expressed the C II TA and IFN-gamma induced the expression of HLA I, II in tumor cells, which were able to express C II TA constitutively.

CONCLUSIONThere is a correlation between the inability of the tumor cells in response to IFN-gamma for HLA expression and the deficiency in the inducible expression of C II TA.

Cell Line, Tumor ; Genes, MHC Class II ; genetics ; HL-60 Cells ; HLA Antigens ; biosynthesis ; genetics ; Humans ; K562 Cells ; Leukemia ; metabolism ; pathology ; Nuclear Proteins ; biosynthesis ; genetics ; Trans-Activators ; biosynthesis ; genetics ; U937 Cells

We examined the effect of class II transactivator (CIITA) down-modulation on allograft rejection. To inhibit the function of CIITA, we constructed a series of CIITA mutants and found one exhibiting the dominant-negative effect on the regulation of major histocompatibility complex (MHC) class II expression. To test whether the CIITA dominant-negative mutant reduces immunogenecity, CIITA-transfected melanoma cells were injected into allogeneic host and assessed for immune evading activity against host immune cells. We demonstrated that the CIITA dominant-negative mutant allowed tumor nodules to develop earlier in the lung than control by this tumor challenge study. Furthermore, skin grafts deficient for CIITA also survived longer than wild-type in allogeneic hosts. Both the tumor challenge and skin graft studies suggest the inhibition of CIITA molecules in donor tissue would be beneficial to the control of allo-response.
Transplantation, Homologous ; Transfection ; Trans-Activators/genetics/*immunology/metabolism ; Trans-Activation (Genetics)/genetics/immunology ; Skin Transplantation ; Nuclear Proteins/genetics/*immunology/metabolism ; Mutation ; Mice, Transgenic ; Mice, Knockout ; Mice, Inbred C57BL ; Mice, Inbred BALB C ; Mice ; Melanoma, Experimental/genetics/immunology/pathology ; Male ; Interferon Type II/pharmacology ; Humans ; Histocompatibility Antigens Class II/genetics/*immunology/metabolism ; Graft Survival/genetics/immunology ; Graft Rejection/genetics/*immunology ; Genes, MHC Class II/genetics/immunology ; Flow Cytometry ; DNA, Complementary/genetics ; Cell Proliferation/drug effects ; Cell Line, Tumor ; Animals