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

Animals ; Female ; Genes, MHC Class I ; Genes, MHC Class II ; Lung ; immunology ; pathology ; Mice ; Mice, Inbred C57BL ; Ovalbumin ; immunology ; Polymerase Chain Reaction ; RNA, Messenger ; analysis

Molecular characterization of swine leukocyte antigen (SLA) genes is important for elucidating the immune responses between swine-donor and human-recipient in xenotransplantation. Examination of associations between alleles of SLA class I genes, type of pig genetic modification, porcine endogenous retrovirus (PERV) viral titer, and PERV subtypes may shed light on the nature of xenograft acceptance or rejection and the safety of xenotransplantation. No significant difference in PERV gag RNA level between transgenic and non-transgenic pigs was noted; likewise, the type of applied transgene had no impact on PERV viremia. SLA-1 gene profile type may correspond with PERV level in blood and thereby influence infectiveness. Screening of pigs should provide selection of animals with low PERV expression and exclusion of specimens with PERV-C in the genome due to possible recombination between A and C subtypes, which may lead to autoinfection. Presence of PERV-C integrated in the genome was detected in 31.25% of specimens, but statistically significant increased viremia in specimens with PERV-C was not observed. There is a need for multidirectional molecular characterization (SLA typing, viremia estimation, and PERV subtype screening) of animals intended for xenotransplantation research in the interest of xeno-recipient safety.
Alleles ; Animals ; Endogenous Retroviruses ; Genes, MHC Class I ; Genes, MHC Class II ; Genome ; Heterografts ; Leukocytes ; Mass Screening ; Recombination, Genetic ; Retroviridae ; RNA ; Swine ; Transgenes ; Transplantation, Heterologous ; Viremia

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

BACKGROUND: As all HLA class II genes, the DQ genes show their polymorphic variation mainly in the second exon, which encodes the first extracellular domain of the molecule. PCR-SSOP (Polymerase chain reaction-Sequence specific oligonucleotide probe) techniques were frequently used for HLA-DQA1 and DQB1 typing but certain alleles, DQA1*0101/0104/0105, *0302/0303, *0501/0505 and DQB1*0201/*0202, which differ from each other in segment other than exon 2, could not be unequivocally assigned. METHODS: To overcome this problem, we applied additional PCR-SSP (PCR-Sequence specific primer) method to analyze DQA1 exons 1, 3 and 4 and DQB1 exon 3. And we investigated the distributions and haplotypes of HLA-DRB1, DQA1 and DQB1 alleles in 406 unrelated Korean healthy individuals. RESULTS: Using this method the indistinguishable alleles of DQA1 and DQB1 in PCR-SSOP were typed definitively. We also found several important associations between DQA1 and DQB1 alleles in the Korean population; DQA1*0101-DQB1*0501, DQA1*0104-DQB1*0502 or -*0503, DQA1 *0105-DQB1*0501, DQA1*0302-DQB1*0303, DQA1*0303-DQB1*0401 or -*0402, DQA1 *0501-DQB1*0201, DQA1*0505-DQB1*0301, and DQA1*0201-DQB1*0202. The haplotypes of DRB1-DQA1-DQB1 associated with DQA1*01, *03, *05, and DQB1*02 subtypes were investigated. Several haplotypes associated with these alleles were observed in the Korean population. CONCLUSION: Our results can be helpful to find potential unrelated donors for bone marrow registries and study the HLA-associated disease and anthropology at high-resolution allelic level.
Alleles ; Anthropology ; Bone Marrow ; Exons ; Genes, MHC Class II ; Haplotypes* ; HLA-DRB1 Chains ; Humans ; Registries ; Unrelated Donors

The objective of study was to investigate the relationship between expressions of CIITA and MHC molecules in five human cell lines. The expressions of MHC molecules and CIITA protein were detected by Western blot, immunohistochemistry and flow cytometry. The expression of CIITA gene was measured by RT-PCR. The results indicated that the expression of MHC-II molecules in 5 human cell lines was consistent with expression of CIITA. The cell lines constitutively expressed CIITA also expressed MHC-II molecules, the expression of MHC-II molecules in cell lines expressed CIITA after induction with IFN-gamma also recovered; the cell lines unexpressed CIITA after induction with IFN-gamma did not respond to IFN-gamma-promoting expression of MHC-II molecules. It is concluded that some cell lines cannot express MHC-II molecules which may be related with deficiency of CIITA expression. It suggest that CIITA participates in regulation of MHC-II molecule expression, which may plays a certain role in escape from carcinogenesis under surveillance of immune system.
Cell Line ; Genes, MHC Class II ; Humans ; Interferon-gamma ; pharmacology ; Nuclear Proteins ; metabolism ; Trans-Activators ; metabolism ; Tumor Cells, Cultured

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

HLA expression is altered in a large variety of human cancers. We performed immunohistochemical staining on tissues from normal, preinvasive, invasive and metastatic cervical cancer tissues using anti-HLA class I or class II antibody. In tissues from normal squamous epithelium, carcinoma in situ (CIS) and microinvasive carcinoma (MIC), the expressions of HLA-B, C heavy chains and class II heavy chain were significantly decreased as disease progressed. When the expression patterns were compared between primary and metastatic squamous cell carcinoma (SCC) lesions, statistically significant down-regulation of HLA class I and class II antigen in metastatic lesions was observed. The rates of HLA-B, C heavy chains and class II heavy chain expressions were all significantly down-regulated compared to the down-regulation rate of class I beta2-microglobulin (beta2m) in invasive squamous lesions, and the expressions of class II heavy chain in metastatic lesions was decreased further than that in primary lesions. Unlike SCC, the degree of HLA class I and class II loss was not evident as disease progressed in early stage of adenocarcinoma. In invasive adenocarcinoma lesions, only the expression of HLA-B, C heavy chains was decreased and no differences were seen in HLA-B, C heavy chain expression patterns between primary and metastatic lesions. These results suggest that alterations of HLA class I and II expressions seem to occur at a particular step in cervical cancer development and depend on tissue types: when the tumor becomes invasive and starts to metastasize.
Antibodies, Monoclonal ; Carcinoma in Situ/immunology/pathology/physiopathology ; Carcinoma, Squamous Cell/immunology/pathology/physiopathology ; Cervix Neoplasms/*immunology/pathology/physiopathology ; Disease Progression ; Female ; Genes, MHC Class I ; Genes, MHC Class II ; HLA Antigens/*analysis ; HLA-B Antigens/analysis ; Histocompatibility Antigens Class I/*analysis ; Histocompatibility Antigens Class II/*analysis ; Human ; Immunohistochemistry ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Support, Non-U.S. Gov't

The intracellular mechanism by which interferon-gamma induces the expression of class II major histocompatibility complex (MHC) antigen in nonlymphoid cells is not clear. The effect of recombinant rat interferon-gamma (IFN-gamma), and cycloheximide on the expression of class II MHC gene was studied using the techniques of immunocytochemical staining and northern blot analysis. IFN-gamma induced de novo transcription of class II MHC gene and class II MHC antigen expression on the cell surface. Cycloheximide did not inhibit IFN-gamma-induced class II MHC antigen expression in a dose-dependent manner indicating translational blockade. These results suggest that IFN-gamma induces class II MHC antigen expression via de novo transcription of class II MHC gene leading to synthesis of new class II MHC molecule.
Animals ; Cell Line ; Cycloheximide/pharmacology ; Gene Expression Regulation/drug effects ; *Genes, MHC Class II ; Interferon-gamma/*pharmacology ; Protein Biosynthesis/drug effects ; Rats ; Transcription, Genetic/*drug effects

Purpose : The main genetic contribution to type 1 diabetes susceptibility is the human leukocyte antigen (HLA) class II gene. Several non-HLA chromosomal regions are also known to be involved. We studied the association of HLA class II and non-HLA candidate genes, which are cytotoxic T lymphocyte antigen-4 (CTLA4), tumor necrosis factor (TNF), lymphotoxin-alpha(LT-alpha, and vitamin D receptor (VDR) gene, polymorphisms with disease susceptibility in Korean children with type 1 diabetes.Methods : Fifty Korean children with type 1 diabetes (29 girls and 21 boys) and 166 healthy Koreans were investigated in this study. HLA class II alleles were determined by PCR-SSP (sequence-specific primer) and PCR-SSOP (sequence specific oliogonucleotide probe) method. CTLA4 exon 1 polymor phism was analyzed by PCR-SSCP (single strand conformation polymorphism), and TNF promotor and LT-alphagene polymorphism by PCR-RFLP (restriction fragment length polymorphism), respectively. VDR gene polymorphisms were analyzed by PCR-RFLP using restriction enzyme FokI, ApaI, TaqI, and BsmI. Results : The frequencies of HLA-DRB1*04, DRB1*09, and DQB1*04 were significantly increased and those of HLA-DRB1*14, DRB1*15, DQB1*05 and DQB1*06 were significantly decreased in the patients with type 1 diabetes compared with the control subjects. No significant differences in the distribution of CTLA4 exon 1, TNF promotor, LT-alpha and VDR gene polymorphisms were observed between the patients with type 1 diabetes and the control subjects. Conclusion : These data suggest that HLA-DRB1*04, DRB1*09, and DQB1*04 are susceptible genes for type 1 diabetes, whereas HLA-DRB1*14, DRB1*15, DQB1*05, and DQB1*06 are protective genes in Korean children. CTLA4 exon 1, TNF promotor, LT-alpha and VDR gene polymorphisms are not associated with susceptibility to type 1 diabetes in Korean children.
Alleles ; Child* ; Diabetes Mellitus, Type 1* ; Disease Susceptibility* ; Exons ; Female ; Genes, MHC Class II ; Humans ; Leukocytes ; Lymphocytes ; Receptors, Calcitriol ; Tumor Necrosis Factor-alpha