scholarly journals Quantification of the relative contribution of major histocompatibility complex (MHC) and non-MHC genes to human immune responses to foreign antigens.

1997 ◽  
Vol 65 (3) ◽  
pp. 872-876 ◽  
Author(s):  
A Jepson ◽  
W Banya ◽  
F Sisay-Joof ◽  
M Hassan-King ◽  
C Nunes ◽  
...  
2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Paweł Karpiński ◽  
Łukasz Łaczmański ◽  
Maria M. Sąsiadek

Current immunotherapies are effective only in a subset of patients, likely due to several factors including defects in tumor cell antigen presentation, decreased response to immune effectors, and molecular heterogeneity of cancers. Recent molecular classifications enable the categorization of many tumor types. However, deregulation of major histocompatibility complex (MHC) gene expression is poorly characterized in the context of molecular cancer subtypes. To suppress the confounding effect of immune infiltrates on expression patterns of immunoregulators, we identified and removed genes with strong correlation to estimated immune compartment levels in each tumor type. Next, we reanalyzed a total of 13 TCGA cancer types encompassing 5651 tumors and 485 normal adjacent tissues by performing unsupervised clustering of 14 MHC genes. Subsequently, resultant clusters were statistically compared in terms of expression of other immune-related genes. Three MHC expression clusters were discovered by unsupervised clustering. We identified concordantly decreased expression of MHC genes (MHC-low) in 26 out of 55 molecular subtypes. Consequently, our study underlines the urgent need for designing strategies to enhance tumor MHC expression that could improve immune cold tumor rejection by cytotoxic T lymphocytes.


2019 ◽  
Vol 22 (1) ◽  
pp. 26-40
Author(s):  
H. Al-Karagoly ◽  
G. Nikbakht ◽  
M. Hassanzadeh ◽  
T. Tolouei

Immune responses to vaccines are mainly influenced by the nature of vaccines and host variation in response to vaccination. In this study we aimed to investigate turkey humoral and cell-mediated immune responses to a Newcastle viscerotropic vaccine and its association with major histocompatibility complex (MHC). Turkeys were vaccinated with Villegas–Glisson/University of Georgia (VG/GA) attenuated vaccine against Newcastle disease. The stimulation index of lymphocyte proliferation and antigen-specific local secretory IgA responses in bile, duodenum, ileum, as well as serum IgY and IgA responses were analysed by enzyme-linked immunosorbent assay. The turkey MHC class II B locus was selected as candidate gene for detection of associations with cellular and humoral immune responses. Significant differences were observed between both cellular and humoral responses of vaccinated and unvaccinated groups. A significant positive correlation was also found between ND specific IgY and ND specific IgA titres in serum, intestine (duodenum and ileum) and trachea. Moreover, the correlation between specific IgA titres in ileum and specific bile, duodenum and trachea was positively significant. High resolution melting analysis (HRM) was used to genotype MHC class II B exon 2. Eight melting profiles (A-G) were identified, among which, profile G showed a significant association with cellular response. The profile B revealed significant association with total IgA titres in serum and ileum. These findings help our understanding of the association of turkey MHC types with immune responses. Further correlation analysis between serum and mucosal antibody titres demonstrated that the levels of IgY and IgA in serum can give an impression about the levels of secretory IgA and situation of mucosal immunity. Based on the significant effects, ND specific IgY in serum appears to be a promising indirect marker for specific IgA in serum and trachea.


2017 ◽  
Vol 10 (2) ◽  
Author(s):  
Anvita Kulshrestha

Several studies related to vertebrates have revealed that highly polymorphic genes within the Major Histocompatibility Complex (MHC) may play a role in mate choice. Females gain direct or indirect fitness benefits by choosing between males with traits that are expressed from good genes, as females can obtain good genes for their offspring by mating with males whose genes are compatible or complementary to their own. There is a tendency for humans to prefer MHC-dissimilar mates, as it would favour the production of heterozygous offspring who would be more resistant to pathogens. This phenomenon has been reviewed on the similar concepts of the influence of MHC genes on human mating preferences, with potential but largely unknown in offspring fitness. The qualitative method can include surveying and interviewing people about their mate choices i.e. females select males with heterozygosity MHC genes over males with homozygous MHC genes. Chi-square test can be performed for statistical analysis. Mating with a MHC dissimilar individual can produce MHC heterozygous offspring that has strong immunocompetence against several parasite types. A heterozygous MHC gene combination has more capability to identify rapidly evolving parasites, which can escape recognition by immune systems containing common alleles.Plusieurs études reliées aux vertébrés ont révélé que les gènes extrêmement polymorphes au sein du complexe majeur d’histocompatibilité (MHC) peuvent jouer un rôle dans le choix d’un partenaire. Les femmes tirent des avantages directs ou indirects de valeur sélective en choisissant entre les hommes dont les traits sont exprimés avec les bons gènes, comme les femmes peuvent obtenir de bons gènes pour leur progéniture par accouplement avec des mâles dont les gènes sont compatibles ou complémentaires à leurs propres. Il y a une tendance pour les humains de préférer les camarades MHC-dissemblables, car ceci favoriserait la production de descendants hétérozygotes qui seraient plus résistants aux pathogènes. Ce phénomène était étudié sur les concepts similairesde l’influence des gènes du MHC sur les préférences d’accouplement humaines, avec un potentiel largement inconnu dans la valeur sélective de la progéniture. La méthode qualitative peut comprendre une enquête et l’interrogation des gens sur leur choix de partenaire, par ex. les femelles choisissent les mâles avec des gènes du CMH hétérozygote sur les hommes ayant des gènes du CMH homozygotes. Le test du chi carré peut être effectué pour faire l’analyse statistique. L’accouplement avec une personne avec un différent CMH peut produire la progéniture CMH hétérozygote qui a une forte immunocompétence contre plusieurs types de parasites. Une combinaison de gènes CMH hétérozygotes a plus de capacité d’identifier les parasites qui évoluent rapidement, qui peuvent échapper à la reconnaissance par le système immunitaire contenant des allèles communs.


1994 ◽  
Vol 180 (5) ◽  
pp. 1911-1920 ◽  
Author(s):  
R S Yeung ◽  
J M Penninger ◽  
T M Kündig ◽  
Y Law ◽  
K Yamamoto ◽  
...  

To reconstitute the human immune system in mice, transgenic mice expressing human CD4 and human major histocompatibility complex (MHC) class II (DQw6) molecules in an endogenous CD4- and CD8-deficient background (mCD4/8-/-), after homologous recombination, have been generated. We report that expression of human CD4 molecule in mCD4/8-/- mice rescues thymocyte development and completely restores the T cell compartment in peripheral lymphoid organs. Upon vesicular stomatitis virus (VSV) challenge, the reconstituted mature T cell population effectively provide T help to B cells in immunoglobulin class switching from IgM to specific IgG-neutralizing antibodies. Human CD4+DQw6+ double transgenic mice are tolerant to DQw6 and the DQw6 molecule functions in antigen presentation, effectively generating a human MHC class II-restricted T cell response to streptococcal M6C2 peptide. These data show that both the hCD4 and DQw6 molecules are functional in mCD4/8-/- mice, fully and stably reconstituting this limb of the human immune system in mice. This animal model provides a powerful in vivo tool to dissect the human CD4-human class II MHC interaction, especially its role in human autoimmune diseases, superantigen-mediated diseases, and acquired immunodeficiency syndrome (AIDS).


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