scholarly journals Impact of Endogenous Intronic Retroviruses on Major Histocompatibility Complex Class II Diversity and Stability

2008 ◽  
Vol 82 (13) ◽  
pp. 6667-6677 ◽  
Author(s):  
Gaby G. M. Doxiadis ◽  
Nanine de Groot ◽  
Ronald E. Bontrop
Keyword(s):  
Major Histocompatibility Complex ◽  
Rhesus Macaques ◽  
Gene Copy Number ◽  
Population Level ◽  
Endogenous Retrovirus ◽  
Copy Number Variations ◽  
Primate Species ◽  
Gene Copy ◽  
Major Histocompatibility ◽  
Histocompatibility Complex

ABSTRACT The major histocompatibility complex (MHC) represents a multigene family that is known to display allelic and gene copy number variations. Primate species such as humans, chimpanzees (Pan troglodytes), and rhesus macaques (Macaca mulatta) show DRB region configuration polymorphism at the population level, meaning that the number and content of DRB loci may vary per haplotype. Introns of primate DRB alleles differ significantly in length due to insertions of transposable elements as long endogenous retrovirus (ERV) and human ERV (HERV) sequences in the DRB2, DRB6, and DRB7 pseudogenes. Although the integration of intronic HERVs resulted sooner or later in the inactivation of the targeted genes, the fixation of these endogenous retroviral segments over long time spans seems to have provided evolutionary advantage. Intronic HERVs may have integrated in a sense or an antisense manner. On the one hand, antisense-oriented retroelements such as HERV-K14I, observed in intron 2 of the DRB7 genes in humans and chimpanzees, seem to promote stability, as configurations/alleles containing these hits have experienced strong conservative selection during primate evolution. On the other hand, the HERVK3I present in intron 1 of all DRB2 and/or DRB6 alleles tested so far integrated in a sense orientation. The data suggest that multigenic regions in particular may benefit from sense introgressions by HERVs, as these elements seem to promote and maintain the generation of diversity, whereas these types of integrations may be lethal in monogenic systems, since they are known to influence transcript regulation negatively.

The role of major histocompatibility complex polymorphisms on SIV infection in rhesus macaques

1996 ◽  
Vol 51 (1-2) ◽  
pp. 35-38 ◽  
Author(s):  
Ronald E. Bontrop ◽  
Nel Otting ◽  
Henk Niphuis ◽  
Riet Noort ◽  
Vera Teeuwsen ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Rhesus Macaques ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Siv Infection

scholarly journals Does intra-individual major histocompatibility complex diversity keep a golden mean?

2008 ◽  
Vol 364 (1513) ◽  
pp. 117-128 ◽  
Author(s):  
Benno Woelfing ◽  
Arne Traulsen ◽  
Manfred Milinski ◽  
Thomas Boehm
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
Adaptive Immune Response ◽  
Population Level ◽  
Current Data ◽  
Small Subset ◽  
Major Histocompatibility ◽  
Mhc Molecules ◽  
Histocompatibility Complex ◽  
Mhc Diversity

An adaptive immune response is usually initiated only if a major histocompatibility complex (MHC) molecule presents pathogen-derived peptides to T-cells. Every MHC molecule can present only peptides that match its peptide-binding groove. Thus, it seems advantageous for an individual to express many different MHC molecules to be able to resist many different pathogens. However, although MHC genes are the most polymorphic genes of vertebrates, each individual has only a very small subset of the diversity at the population level. This is an evolutionary paradox. We provide an overview of the current data on infection studies and mate-choice experiments and conclude that overall evidence suggests that intermediate intra-individual MHC diversity is optimal. Selective forces that may set an upper limit to intra-individual MHC diversity are discussed. An updated mathematical model based on recent findings on T-cell selection can predict the natural range of intra-individual MHC diversity. Thus, the aim of our review is to evaluate whether the number of MHC alleles usually present in individuals may be optimal to balance the advantages of presenting an increased range of peptides versus the disadvantages of an increased loss of T-cells.

Major Histocompatibility Complex class IIDQdiversity in Rhesus macaques

1993 ◽  
Vol 41 (4) ◽  
pp. 178-185 ◽  
Author(s):  
Bastiaan L. Slierendregt ◽  
Nel Otting ◽  
Margreet Jonker ◽  
Ronald E. Bontrop
Keyword(s):  
Major Histocompatibility Complex ◽  
Major Histocompatibility Complex Class ◽  
Rhesus Macaques ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Histocompatibility Complex

scholarly journals Immunization with recombinant macaque major histocompatibility complex class I and II and human immunodeficiency virus gp140 inhibits simian–human immunodeficiency virus infection in macaques

2012 ◽  
Vol 93 (7) ◽  
pp. 1506-1518 ◽  
Author(s):  
Gui-Bo Yang ◽  
Yufei Wang ◽  
Kaboutar Babaahmady ◽  
Jørgen Schøller ◽  
Durdana Rahman ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Major Histocompatibility Complex ◽  
Rhesus Macaques ◽  
Class I ◽  
Major Histocompatibility ◽  
Viral Loads ◽  
Histocompatibility Complex ◽  
Immunodeficiency Virus ◽  
Peak Viral Load ◽  
Hiv Gp120

Genetic, epidemiological and experimental evidence suggest that the major histocompatibility complex (MHC) is critical in controlling human immunodeficiency virus (HIV) infection. The objectives of this study were to determine whether novel recombinant Mamu MHC constructs would elicit protection against rectal challenge with heterologous simian–human immunodeficiency virus (SHIV) strain SF162.P4 in rhesus macaques. Mamu class I and II gene products were linked together with HIV gp140, simian immunodeficiency virus (SIV) p27 and heat-shock protein 70 to dextran. The vaccine was administered to two groups, each consisting of nine macaques, either subcutaneously (SC), or rectally and boosted by SC immunization. The controls were untreated or adjuvant-treated animals. Repetitive rectal challenges with up to ten doses of SHIV SF162.P4 showed a significant decrease in the peak and sequential viral RNA concentrations, and three macaques remained uninfected, in the nine SC-immunized animals, compared with infection in all nine controls. Macaques immunized rectally followed by SC boosters showed a less significant decrease in both sequential and peak viral loads compared with the SC-immunized animals, and all were infected following rectal challenge with SHIV SF162.P4. Plasma and mucosal IgG and IgA antibodies to Mamu class I alleles and HIV gp120, as well as to RANTES (regulated upon activation, normal T-cell expressed, and secreted; CCR5) were increased, and showed significant inverse correlations with the peak viral load. These results suggested that allo-immunization with recombinant MHC constructs linked to HIV–SIV antigens merits further investigation in preventing HIV-1 infection.

scholarly journals INITIAL CHARACTERIZATION OF MAJOR HISTOCOMPATIBILITY COMPLEX (MHC) CLASS IIB EXON 2 IN AN ENDANGERED RATTLESNAKE, THE EASTERN MASSASAUGA (SISTRURUS CATENATUS)

2014 ◽  
pp. 98-104 ◽  
Author(s):  
Collin P. Jaeger ◽  
Richard B. King ◽  
Melvin R. Duvall
Keyword(s):  
Major Histocompatibility Complex ◽  
Positive Selection ◽  
Balancing Selection ◽  
Population Level ◽  
Major Histocompatibility ◽  
Exon 2 ◽  
Conservation Implications ◽  
Histocompatibility Complex ◽  
Sistrurus Catenatus ◽  
Mhc Class Iib

Genes of the major histocompatibility complex (MHC) play an important role in the vertebrate immune system and exhibit remarkably high levels of polymorphism, maintained by strong balancing selection. While the conservation implications of MHC variation have been explored in a variety of vertebrates, non-avian reptiles (most notably snakes) have received less attention. To address this gap and take the first steps toward more extensive population-level analyses, we cloned and sequenced MHC IIB exon 2 in an endangered rattlesnake, the Eastern Massasauga (Sistrurus catenatus). Based on three individuals, we found evidence of at least four putatively functional loci. These sequences exhibited relatively high levels of variation and significantly higher rates of nonsynonymous to synonymous substitutions, especially within the antigen-binding sites, indicating strong positive selection. Phylogenetic analysis revealed a pattern of trans-species polymorphism, also suggesting positive selection. These results contribute to our understanding of MHC variation in non-avian reptiles and form a basis for more studies of MHC variation in snakes of conservation concern.

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