scholarly journals Within-trio tests provide little support for post-copulatory selection on major histocompatibility complex haplotypes in a free-living population

2021 ◽  
Vol 288 (1945) ◽  
pp. 20202862
Author(s):  
W. Huang ◽  
J. M. Pemberton
Keyword(s):  
Major Histocompatibility Complex ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Ovis Aries ◽  
Transmission Ratio Distortion ◽  
Transmission Ratio ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Ratio Distortion ◽  
Mhc Class Ii Genes

Sexual selection has been proposed as a force that could help maintain the diversity of major histocompatibility complex (MHC) genes in vertebrates. Potential selective mechanisms can be divided into pre-copulatory and post-copulatory, and in both cases, the evidence for occurrence is mixed, especially in natural populations. In this study, we used a large number of parent-offspring trios that were diplotyped for MHC class II genes in a wild population of Soay sheep ( Ovis aries ) to examine whether there was within-trio post-copulatory selection on MHC class II genes at both the haplotype and diplotype levels. We found there was transmission ratio distortion of one of the eight MHC class II haplotypes (E) which was transmitted less than expected by fathers, and transmission ratio distortion of another haplotype (A) which was transmitted more than expected by chance to male offspring. However, in both cases, these deviations were not significant after correction for multiple tests. In addition, we did not find any evidence of post-copulatory selection at the diplotype level. These results imply that, given known parents, there is no strong post-copulatory selection on MHC class II genes in this population.

scholarly journals Developmental extinction of major histocompatibility complex class II gene expression in plasmocytes is mediated by silencing of the transactivator gene CIITA.

1994 ◽  
Vol 180 (4) ◽  
pp. 1329-1336 ◽  
Author(s):  
P Silacci ◽  
A Mottet ◽  
V Steimle ◽  
W Reith ◽  
B Mach
Keyword(s):  
Gene Expression ◽  
Major Histocompatibility Complex ◽  
B Lymphocytes ◽  
Mhc Class Ii ◽  
Plasma Cells ◽  
Terminal Differentiation ◽  
Class Ii ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Mhc Class Ii Genes

Constitutive major histocompatibility complex (MHC) class II gene expression is tightly restricted to antigen presenting cells and is under developmental control. Cells of the B cell lineage acquire the capacity to express MHC class II genes early during ontogeny and lose this property during terminal differentiation into plasma cells. Cell fusion experiments have suggested that the extinction of MHC class II expression in plasma cells is due to a dominant repression, but the underlying mechanisms are not understood. CIITA was recently identified as an MHC class II transactivator that is essential for MHC class II expression in B lymphocytes. We show here that inactivation of MHC class II genes in plasmocytes is associated with silencing of the CIITA gene. Moreover, experimentally induced expression of CIITA in plasmocytes leads to reexpression of MHC class II molecules to the same level as that observed on B lymphocytes. We therefore conclude that the loss of MHC class II expression observed upon terminal differentiation of B lymphocytes into plasmocytes results from silencing of the transactivator gene CIITA.

scholarly journals A Mechanism for the Major Histocompatibility Complex–linked Resistance to Autoimmunity

1997 ◽  
Vol 186 (7) ◽  
pp. 1059-1075 ◽  
Author(s):  
Dennis Schmidt ◽  
Joan Verdaguer ◽  
Nuzhat Averill ◽  
Pere Santamaria
Keyword(s):  
Major Histocompatibility Complex ◽  
Mhc Class Ii ◽  
Pancreatic Beta Cell ◽  
Nod Mice ◽  
Class Ii ◽  
Major Histocompatibility ◽  
Nonobese Diabetic ◽  
Histocompatibility Complex ◽  
Nonobese Diabetic Mice ◽  
Mhc Class Ii Genes

Certain major histocompatibility complex (MHC) class II haplotypes encode elements providing either susceptibility or dominant resistance to the development of spontaneous autoimmune diseases via mechanisms that remain undefined. Here we show that a pancreatic beta cell–reactive, I-Ag7–restricted, transgenic TCR that is highly diabetogenic in nonobese diabetic mice (H-2g7) undergoes thymocyte negative selection in diabetes-resistant H-2g7/b, H-2g7/k, H-2g7/q, and H-2g7/nb1 NOD mice by engaging antidiabetogenic MHC class II molecules on thymic bone marrow–derived cells, independently of endogenous superantigens. Thymocyte deletion is complete in the presence of I-Ab, I-Ak + I-Ek or I-Anb1 + I-Enb1 molecules, partial in the presence of I-Aq or I-Ak molecules alone, and absent in the presence of I-As molecules. Mice that delete the transgenic TCR develop variable degrees of insulitis that correlate with the extent of thymocyte deletion, but are invariably resistant to diabetes development. These results provide an explanation as to how protective MHC class II genes carried on one haplotype can override the genetic susceptibility to an autoimmune disease provided by allelic MHC class II genes carried on a second haplotype.

scholarly journals Functional complementation of major histocompatibility complex class II regulatory mutants by the purified X-box-binding protein RFX.

1994 ◽  
Vol 14 (10) ◽  
pp. 6839-6847 ◽  
Author(s):  
B Durand ◽  
M Kobr ◽  
W Reith ◽  
B Mach
Keyword(s):  
Major Histocompatibility Complex ◽  
Mhc Class Ii ◽  
Class Ii ◽  
In Vitro Transcription ◽  
Major Histocompatibility ◽  
Transcription System ◽  
Histocompatibility Complex ◽  
Complementation Groups ◽  
Mhc Class Ii Genes

Major histocompatibility complex (MHC) class II deficiency, or bare lymphocyte syndrome (BLS), is a disease of gene regulation. Patients with BLS have been classified into at least three complementation groups (A, B, and C) believed to correspond to three distinct MHC class II regulatory genes. The elucidation of the molecular basis for this disease will thus clarify the mechanisms controlling the complex regulation of MHC class II genes. Complementation groups B and C are characterized by a lack of binding of RFX, a nuclear protein that normally binds specifically to the X box cis-acting element present in the promoters of all MHC class II genes. We have now purified RFX to near homogeneity by affinity chromatography. Using an in vitro transcription system based on the HLA-DRA promoter, we show here that extracts from RFX-deficient cells from patients with BLS (BLS cells) in groups B and C, which are transcriptionally inactive in this assay, can be complemented to full transcriptional activity by the purified RFX. As expected, purified RFX also restores a completely normal pattern of X box-binding complexes in these mutant extracts. This provides the first direct functional evidence that RFX is an activator of MHC class II gene transcription and that its absence is indeed responsible for the regulatory defect in MHC class II gene expression in patients with BLS.

Functional complementation of major histocompatibility complex class II regulatory mutants by the purified X-box-binding protein RFX

1994 ◽  
Vol 14 (10) ◽  
pp. 6839-6847
Author(s):  
B Durand ◽  
M Kobr ◽  
W Reith ◽  
B Mach
Keyword(s):  
Major Histocompatibility Complex ◽  
Mhc Class Ii ◽  
Class Ii ◽  
In Vitro Transcription ◽  
Major Histocompatibility ◽  
Transcription System ◽  
Histocompatibility Complex ◽  
Complementation Groups ◽  
Mhc Class Ii Genes

Major histocompatibility complex (MHC) class II deficiency, or bare lymphocyte syndrome (BLS), is a disease of gene regulation. Patients with BLS have been classified into at least three complementation groups (A, B, and C) believed to correspond to three distinct MHC class II regulatory genes. The elucidation of the molecular basis for this disease will thus clarify the mechanisms controlling the complex regulation of MHC class II genes. Complementation groups B and C are characterized by a lack of binding of RFX, a nuclear protein that normally binds specifically to the X box cis-acting element present in the promoters of all MHC class II genes. We have now purified RFX to near homogeneity by affinity chromatography. Using an in vitro transcription system based on the HLA-DRA promoter, we show here that extracts from RFX-deficient cells from patients with BLS (BLS cells) in groups B and C, which are transcriptionally inactive in this assay, can be complemented to full transcriptional activity by the purified RFX. As expected, purified RFX also restores a completely normal pattern of X box-binding complexes in these mutant extracts. This provides the first direct functional evidence that RFX is an activator of MHC class II gene transcription and that its absence is indeed responsible for the regulatory defect in MHC class II gene expression in patients with BLS.

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