scholarly journals The multigenic structure of the MHC locus contributes to positive selection efficiency: A role for MHC class II gene-specific restriction

2005 ◽  
Vol 35 (12) ◽  
pp. 3622-3630 ◽  
Author(s):  
Miguel Caetano Monteiro ◽  
Sofia Couceiro ◽  
Carlos Penha-Gonçalves
Keyword(s):  
Positive Selection ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Selection Efficiency ◽  
Specific Restriction ◽  
Mhc Locus

Evolution of MHC class II SLA-DRB1 locus in the Croatian wild boar (Sus scrofa ) implies duplication and weak signals of positive selection

2018 ◽  
Vol 50 (1) ◽  
pp. 33-41
Author(s):  
H. Arbanasić ◽  
D. Konjević ◽  
L. Vranković ◽  
M. Bujanić ◽  
S. Stipoljev ◽  
...  
Keyword(s):  
Positive Selection ◽  
Wild Boar ◽  
Mhc Class Ii ◽  
Sus Scrofa ◽  
Class Ii ◽  
Weak Signals ◽  
Drb1 Locus

Positive selection of CD4+ thymocytes controlled by MHC class II gene products

Nature ◽  
1988 ◽  
Vol 336 (6198) ◽  
pp. 471-473 ◽  
Author(s):  
H. Robson MacDonald ◽  
Rosemary K. Lees ◽  
Reto Schneider ◽  
Rolf M. Zinkernagel ◽  
Hans Hengartner
Keyword(s):  
Positive Selection ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Gene Products ◽  
Selection Of

scholarly journals Comparison of peptides bound to spleen and thymus class II.

1993 ◽  
Vol 178 (6) ◽  
pp. 2173-2183 ◽  
Author(s):  
P Marrack ◽  
L Ignatowicz ◽  
J W Kappler ◽  
J Boymel ◽  
J H Freed
Keyword(s):  
Positive Selection ◽  
Mhc Class Ii ◽  
Class Ii ◽  
The Past ◽  
Histocompatibility Complex ◽  
Specific Distribution ◽  
Class Ii Mhc ◽  
Beta Receptors ◽  
Self Peptides ◽  
Selection Of

In the past we and others have suggested that positive selection of developing thymocytes may depend upon interaction between the alpha beta receptors on these cells and major histocompatibility complex (MHC) proteins bound to peptides found uniquely in the selecting tissue, thymus cortical epithelium. To test this hypothesis, peptides were isolated from MHC class II proteins of spleen, thymus cortical plus medullary epithelium, or thymus cortical epithelium alone. The results showed that the major peptides bound to class II on thymus cortical epithelium were also associated with spleen class II. Some peptides could only be detected in isolates from spleen, probably because of differences in the distribution or uptake of the donor proteins between spleen and thymus. Thus, although we found some tissue-specific distribution of self-peptides, our data suggest that there are no fundamental differences among these tissues in the occupancy of class II MHC by self-peptides. These results limit hypotheses which depend on a specialized mechanism of peptide generation and/or MHC class II loading to account for the positive selection of T cells on thymic cortical epithelium.

scholarly journals Evidence for Distinct Mechanisms in the Shaping of the CD4 T Cell Repertoire in Histologically Distinct Myasthenia Gravis – Associated Thymomas

2001 ◽  
Vol 8 (3-4) ◽  
pp. 279-290 ◽  
Author(s):  
P. Ströbel ◽  
M. Helmreich ◽  
H. Kalbacher ◽  
H. K. Müller-Hermelink ◽  
A. Marx
Keyword(s):  
T Cell ◽  
Myasthenia Gravis ◽  
Positive Selection ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Tumor Subtype ◽  
Cell Repertoire ◽  
Well Differentiated ◽  
The One ◽  
T Cell Maturation

The major histocompatibility complex (MHC) class II is involved both in thymocyte maturation and peptide presentation and might thus play a key role in the pathogenesis of paraneoplastic myasthenia gravis (MG) in thymomas. To further investigate this issue, we analyzed and scored the expression of epithelial class II expression in 35 thymomas (medullary, MDT; mixed, MXT; cortical and well differentiated thymic carcinoma, CT / WDTC) and correlated it with the histological tumor subtype, prevalence of MG and thymocyte maturation, which was analyzed by flow cytometry and RT-PCR. Our results show that both MHC class II expression and thymocyte maturation are highly dependent on the histological tumor subtype. CT / WDTC retain features of the normal outer thymic cortex, namely substantial MHC class II expression together with normal early thymocyte maturation until late phases of positive selection, but disturbed terminal thymopoiesis. By contrast, MDT and MXT retain features of the normal inner cortex and the medulla with low to absent class II expression and highly abnormal early thymocyte maturation including impaired positive selection, while terminal T cell maturation in MXT appeared undisturbed. There was no correlation between MHC class II expression and MG status for a given tumor subtype. In conclusion, our results provide evidence for a different histogenesis of cortical thymomas and well differentiated carcinomas on the one hand and mixed and medullary thymomas on the other.Decreased expression levels of MHC class II, although of crucial importance for abnormal intratumorous maturation, are not sufficient to explain the emergence of paraneoplastic MG.

scholarly journals Genetic diversity, evolution and selection in the major histocompatibility complex DRB and DQB loci in the family Equidae

BMC Genomics ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Marie Klumplerova ◽  
Petra Splichalova ◽  
Jan Oppelt ◽  
Jan Futas ◽  
Aneta Kohutova ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Major Histocompatibility Complex ◽  
Positive Selection ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Depth Analysis ◽  
The Family ◽  
Antigen Presenting

Abstract Background The mammalian Major Histocompatibility Complex (MHC) is a genetic region containing highly polymorphic genes with immunological functions. MHC class I and class II genes encode antigen-presenting molecules expressed on the cell surface. The MHC class II sub-region contains genes expressed in antigen presenting cells. The antigen binding site is encoded by the second exon of genes encoding antigen presenting molecules. The exon 2 sequences of these MHC genes have evolved under the selective pressure of pathogens. Interspecific differences can be observed in the class II sub-region. The family Equidae includes a variety of domesticated, and free-ranging species inhabiting a range of habitats exposed to different pathogens and represents a model for studying this important part of the immunogenome. While equine MHC class II DRA and DQA loci have received attention, the genetic diversity and effects of selection on DRB and DQB loci have been largely overlooked. This study aimed to provide the first in-depth analysis of the MHC class II DRB and DQB loci in the Equidae family. Results Three DRB and two DQB genes were identified in the genomes of all equids. The genes DRB2, DRB3 and DQB3 showed high sequence conservation, while polymorphisms were more frequent at DRB1 and DQB1 across all species analyzed. DQB2 was not found in the genome of the Asiatic asses Equus hemionus kulan and E. h. onager. The bioinformatic analysis of non-zero-coverage-bases of DRB and DQB genes in 14 equine individual genomes revealed differences among individual genes. Evidence for recombination was found for DRB1, DRB2, DQB1 and DQB2 genes. Trans-species allele sharing was identified in all genes except DRB1. Site-specific selection analysis predicted genes evolving under positive selection both at DRB and DQB loci. No selected amino acid sites were identified in DQB3. Conclusions The organization of the MHC class II sub-region of equids is similar across all species of the family. Genomic sequences, along with phylogenetic trees suggesting effects of selection as well as trans-species polymorphism support the contention that pathogen-driven positive selection has shaped the MHC class II DRB/DQB sub-regions in the Equidae.

scholarly journals Positive selection of thymocytes induced by gene transfer: MHC class II-mediated selection of CD8 lineage cells

1999 ◽  
Vol 11 (10) ◽  
pp. 1595-1600 ◽  
Author(s):  
Ronald Rooke ◽  
Caroline Waltzinger ◽  
Christophe Benoist ◽  
Diane Mathis
Keyword(s):  
Gene Transfer ◽  
Positive Selection ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Selection Of

scholarly journals Positive Selection by Purified MHC Class II / Thymic Epithelial CellsIn Vitro: Costimulatory Signals Mediated by B7 Are Not Involved

1994 ◽  
Vol 3 (4) ◽  
pp. 265-271 ◽  
Author(s):  
Eric J. Jenkinson ◽  
Graham Anderson ◽  
Nel C. Moore ◽  
Christopher A. Smith ◽  
John J. T. Owen
Keyword(s):  
T Cells ◽  
Epithelial Cells ◽  
Positive Selection ◽  
Mhc Class Ii ◽  
Functional Capacity ◽  
T Cell Development ◽  
Class Ii ◽  
Thymic Epithelial Cells ◽  
Costimulatory Signals

We have investigated the possibility that the costimulatory signals required for activation of mature T cells also play a role in providing differentiation signals for positive selection during T-cell development. We show that purified MHC Class II+thymic epithelial cells are able to support positive selectionin vitrobut lack both the functional capacity to deliver costimulatory signals and expression of the costimulatory ligand B7. Our results suggest that the additional signals provided by costimulatory ligands are not required for TCR-mediated positive selection, although other ancillary signals provided by thymic epithelial cells may be involved.

scholarly journals Deficient Positive Selection of CD4 T Cells in Mice Displaying Altered Repertoires of MHC Class II–Bound Self-Peptides

Immunity ◽  
1997 ◽  
Vol 7 (2) ◽  
pp. 197-208 ◽  
Author(s):  
Catherine E Grubin ◽  
Susan Kovats ◽  
Paul deRoos ◽  
Alexander Y Rudensky
Keyword(s):  
T Cells ◽  
Positive Selection ◽  
Mhc Class Ii ◽  
Cd4 T Cells ◽  
Class Ii ◽  
Self Peptides ◽  
Selection Of

scholarly journals HLA-DRB1*11 and variants of the MHC class II locus are strong risk factors for systemic juvenile idiopathic arthritis

2015 ◽  
Vol 112 (52) ◽  
pp. 15970-15975 ◽  
Author(s):  
Michael J. Ombrello ◽  
Elaine F. Remmers ◽  
Ioanna Tachmazidou ◽  
Alexei Grom ◽  
Dirk Foell ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Mhc Class Ii ◽  
Meta Analysis ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Class Ii ◽  
European Ancestry ◽  
Life Threatening ◽  
Bona Fide ◽  
Mhc Locus ◽  
Hla Dqa1

Systemic juvenile idiopathic arthritis (sJIA) is an often severe, potentially life-threatening childhood inflammatory disease, the pathophysiology of which is poorly understood. To determine whether genetic variation within the MHC locus on chromosome 6 influences sJIA susceptibility, we performed an association study of 982 children with sJIA and 8,010 healthy control subjects from nine countries. Using meta-analysis of directly observed and imputed SNP genotypes and imputed classic HLA types, we identified the MHC locus as a bona fide susceptibility locus with effects on sJIA risk that transcended geographically defined strata. The strongest sJIA-associated SNP, rs151043342 [P = 2.8 × 10−17, odds ratio (OR) 2.6 (2.1, 3.3)], was part of a cluster of 482 sJIA-associated SNPs that spanned a 400-kb region and included the class II HLA region. Conditional analysis controlling for the effect of rs151043342 found that rs12722051 independently influenced sJIA risk [P = 1.0 × 10−5, OR 0.7 (0.6, 0.8)]. Meta-analysis of imputed classic HLA-type associations in six study populations of Western European ancestry revealed that HLA-DRB1*11 and its defining amino acid residue, glutamate 58, were strongly associated with sJIA [P = 2.7 × 10−16, OR 2.3 (1.9, 2.8)], as was the HLA-DRB1*11—HLA-DQA1*05—HLA-DQB1*03 haplotype [6.4 × 10−17, OR 2.3 (1.9, 2.9)]. By examining the MHC locus in the largest collection of sJIA patients assembled to date, this study solidifies the relationship between the class II HLA region and sJIA, implicating adaptive immune molecules in the pathogenesis of sJIA.

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