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

<b>OBJECTIVEb>To investigate the association of HLA class I and II alleles with generalized vitiligo in ethnic Han Chinese in north China.

<b>METHODSb>By 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.

<b>RESULTSb>The 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.

<b>CONCLUSIONb>These 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

BACKGROUND: A large number of diseases occur in association with specific HLA-B or-C alleles. Recently a new gene, termed maj or histocompatibility complex class I chain-related gene A (MICA), has been identified in close proximity to HLA-B. The function of this gene is still unknown. However, it is structurally similar to HLA class I genes. MICA gene is polymorphic and is potentially associated with several diseases. METHODS: To evaluate the association of MICA gene in Korean patient s with human immunodeficiency virus 1 (HIV-1) infections, Polymerase chain reaction-Sequence specific primer (PCR-SSP) was done for MICA alleles in the extracellular exons, and a microsatellite analysis for GCT repeat polymorphisms in the TM exon was also completed. RESULTS: In 199 Korean healthy controls, 7 alleles were observed and the frequencies for each allele were MICA008 (44.7%), MICA0 10 (34.2%), MICA002 (31.7%), MICA004 (23.6%), MICA0 12 (2 1.6%), MICA009 (19.6%), and MICA007 (6.5%). When 65 HIV seropositive patients were analyzed, MICA007 allele frequency was significantly higher than in controls (15.4% vs 6.5 %, RR=2.6, p<0.04). In contrast, the frequencies of other MICA alleles and microsatellite alleles in the transmembrane region of MICA gene were not significantly different between HIV seropositive patients and controls. The tight linkage between MICA alleles in the extracellular exons and GCT repeat polymorphisms in the TM exon was observed as follows; MICA002/A9, MICA004/A6, MICA007/A4, MICA008/A5. 1, MICA0 10/A5, and MICA0 12/A4 in both groups. No significant difference between patient s and controls was observed in the haplotype frequencies of MICA alleles in the extracellular exons and GCT repeat polymorphisms in the TM exon. CONCLUSION: The data suggest that immune functions related with MICA gene may affect a HIV infections.
Alleles ; Exons ; Gene Frequency ; Genes, MHC Class I ; Haplotypes ; HIV Infections* ; HIV* ; HIV-1 ; HLA-B Antigens ; Humans ; Major Histocompatibility Complex ; Microsatellite Repeats

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

<b>OBJECTIVEb>To evaluate the efficiency of the BIOMED-2 PCR assay and its implication in the diagnosis of mature B-cell non-Hodgkin's lymphomas.

<b>METHODSb>Clinical, morphological and immunohistochemical features of 72 cases of non-Hodgkin's lymphomas were studied, including 25 reactive lymphoid hyperplasia, 37 diffuse large B cell lymphomas (DLBCL) and 35 extranodal marginal zone lymphomas of mucosa associated lymphoid tissues (MALT lymphoma and in addition, 25 cases of reactive lymphoid hyperplasia were used as the controls). DNA was exacted from the paraffin embedded formalin fixed tissue blocks and the quality of DNA was assessed using the BIOMED-2 specimen control reaction. Adequate samples were then analyzed by BIOMED-2 for immunoglobulin heavy and kappa light chain rearrangements.

<b>RESULTSb>Adequate DNA was obtained in 83 of 97 samples, including 60 mature B cell lymphomas and 23 reactive lymphoid hyperplasia. Clonal B-cell gene rearrangements were detected in 57 of 60 (95%) lymphomas. In contrast, clonal Ig gene rearrangements were not detected in any of the 23 cases of reactive lymphoid hyperplasia.

<b>CONCLUSIONb>BIOMED-2 assay is highly sensitive and specific for the detection of clonal B cell gene rearrangement using routine paraffin embedded formalin fixed specimens.

Antigens, CD20 ; metabolism ; CD79 Antigens ; metabolism ; DNA, Neoplasm ; genetics ; Gene Rearrangement, B-Lymphocyte ; genetics ; Gene Rearrangement, B-Lymphocyte, Heavy Chain ; genetics ; Gene Rearrangement, B-Lymphocyte, Light Chain ; genetics ; Genes, Immunoglobulin ; Humans ; Immunophenotyping ; Lymphoma, B-Cell ; genetics ; immunology ; pathology ; Lymphoma, B-Cell, Marginal Zone ; genetics ; immunology ; pathology ; Lymphoma, Large B-Cell, Diffuse ; genetics ; immunology ; pathology ; Paraffin Embedding ; Pseudolymphoma ; genetics ; immunology ; pathology ; Sensitivity and Specificity

The immune system of mammalian has developed sophisticated mechanism to deal with diverse unknown antigens by random rearrangement of V, D and J antigen gene fragments. The immune self-tolerance is the mechanism to avoid self-destruction by the gene rearrangement generated autoreactive lymphocytes. Until recently it was believed that autoreactive lymphocytes are either deleted or rendered unable to respond by the supposed cell or clone selection mechanism. However, recent findings from a number of laboratories suggest instead of cell selection but receptor selection plays an essential role in immune self-tolerance. Receptor selection is carried out by secondary or nested rearrangement of antigen receptor gene fragments, and can occur at different stages of lymphocyte differentiation. Furthermore, secondary rearrangement of receptor gene also plays an important role in shaping immune response after the interaction of receptor with antigen by altering its specificity.
Autoimmune Diseases ; immunology ; B-Lymphocytes ; immunology ; Gene Rearrangement, B-Lymphocyte ; immunology ; Genes, Immunoglobulin ; Humans ; Immune Tolerance ; Receptors, Antigen, B-Cell ; immunology ; Self Tolerance ; immunology

No abstract available.
Aggressive Periodontitis* ; Immunogenetics* ; Immunoglobulin Allotypes ; Immunoglobulin G*